Thalamic connectivity topography in newborns with spina bifida: association with neurological functional level but not developmental outcome at 2 years.

Spina bifida affects spinal cord and cerebral development, leading to motor and cognitive delay. We investigated whether there are associations between thalamocortical connectivity topography, neurological function, and developmental outcomes in open spina bifida. Diffusion tensor MRI was used to assess thalamocortical connectivity in 44 newborns with open spina bifida who underwent prenatal surgical repair. We quantified the volume of clusters formed based on the strongest probabilistic connectivity to the frontal, parietal, and temporal cortex. Developmental outcomes were assessed using the Bayley III Scales, while the functional level of the lesion was assessed by neurological examination at 2 years of age. Higher functional level was associated with smaller thalamo-parietal, while lower functional level was associated with smaller thalamo-temporal connectivity clusters (Bonferroni-corrected P < 0.05). Lower functional levels were associated with weaker thalamic temporal connectivity, particularly in the ventrolateral and ventral anterior nuclei. No associations were found between thalamocortical connectivity and developmental outcomes. Our findings suggest that altered thalamocortical circuitry development in open spina bifida may contribute to impaired lower extremity function, impacting motor function and independent ambulation. We hypothesize that the neurologic function might not merely be caused by the spinal cord lesion, but further impacted by the disruption of cerebral neuronal circuitry.

Processing Speed Partially Mediates Executive Function Impairments in Adolescents with Congenital Heart Disease: Results from a Prospective Cohort Study.

OBJECTIVE: To assess processing speed, fine motor function, attention, and executive function (EF) impairments in adolescents with complex congenital heart disease (CHD) who underwent open-heart surgery during infancy. STUDY DESIGN: We administered a comprehensive neuropsychological test battery evaluating 5 EF domains: working memory, inhibition, cognitive flexibility, fluency, and planning and primary neurodevelopmental processes (PNPs): processing speed, fine motor function, and attention. The sample included 100 adolescents with complex CHD from a previous University Children's Hospital Zurich study, with 104 healthy controls for comparison. We generated scores for each EF domain and computed an EF summary score. Group comparisons and associations were analyzed with multiple regressions accounting for parental education. Mediation analysis explored how PNPs mediate the effect between a CHD diagnosis and EF. RESULTS: In adolescents with complex CHD, all EF domains and the EF summary score were impaired (ß = 0.20 to 0.37, all P < .05). Furthermore, they exhibited slower processing speed (ß = 0.27, P < .01) than healthy controls, with no differences in attention (ß = -0.07, P = .34) and fine motor function (ß = 0.08, P = .34). Processing speed showed a strong association with the EF summary score (ß = 0.60, P < .001) and partially mediated the relationship between CHD diagnosis and the EF summary score (ß = 0.37, 95% CI [0.24, 0.50], P < .001). CONCLUSION: Adolescents with complex CHD show difficulties in EFs and processing speed. Notably, processing speed is strongly associated with EFs and partly accounts for EFs disparities between patients and healthy controls. Early detection and interventions for processing speed difficulties may improve EF outcomes in these patients.

Heart rate variability and cognitive functions in adolescents with complex congenital heart disease.

BACKGROUND: Heart Rate Variability (HRV) originates from the interplay between parasympathetic/sympathetic inputs to the heart, thus serving as an indicator of Autonomic Nervous System regulation. Prior research indicates that decreased HRV, marked by reduced autonomic balance, is related to poorer cognitive performance. While the population with congenital heart disease (CHD) show changes in HRV linked with the heart defect, the association between HRV and cognitive functions in CHD remains unexplored. METHODS: 46 adolescents with CHD who went through infant open-heart surgery and 64 healthy controls (50.9% males, 12.8 ± 1.4 years) underwent neurodevelopmental testing and photoplethysmograph acquisition. Group differences and associations with cognitive functions were analysed with linear regression. P values were FDR-corrected. RESULTS: Adolescents with CHD showed lower HRV (quantified by high-frequency power) compared to controls (p < 0.001). Lower HRV was correlated with worse executive function (ß = 0.24, p = 0.044) and lower IQ (ß = 0.26, p = 0.010) in the whole sample and with lower IQ (ß = 0.35, p = 0.014) in the CHD group. These associations were robust to confounders, including age, sex, and socioeconomic status. CONCLUSION: Our findings demonstrate an association between HRV and cognitive functions in adolescents with complex CHD. Early detection of alterations in HRV/autonomic regulation may help to identify children with CHD at risk for cognitive impairments. IMPACT: Adolescents with congenital heart disease (CHD) showed lower heart rate variability (HRV), indicating an imbalanced autonomic nervous system. Lower HRV was associated with lower IQ and executive function (EF) in the whole sample. The association between HRV and IQ was significantly stronger in CHD than in healthy controls. This study provides the first evidence of a link between altered HRV and cognitive impairments in the CHD population. Neurodevelopmental impairments seen in adolescents with CHD could be linked to their altered cardiac autonomic nervous activity, marked by low HRV.

Effects of hemodynamic alterations and oxygen saturation on cerebral perfusion in congenital heart disease.

BACKGROUND: Patients with severe congenital heart disease (CHD) are at risk for neurodevelopmental impairment. An abnormal cerebral blood supply caused by the altered cardiac physiology may limit optimal brain development. The aim of this study was to evaluate the effect of a systemic-to-pulmonary shunt, aortic arch obstruction and arterial oxygen saturation on cerebral perfusion in patients with severe CHD. METHODS: Patients with severe CHD requiring cardiac surgery within the first six weeks of life, who underwent pre- and/or postoperative brain magnetic resonance imaging (MRI), and healthy controls with one postnatal scan were included. Cerebral perfusion in deep and cortical gray matter was assessed by pseudocontinuous arterial spin labeling MRI. RESULTS: We included 59 CHD and 23 healthy control scans. The presence of a systemic-to-pulmonary shunt was associated with decreased perfusion in cortical (p = 0.003), but not in deep gray matter (p = 0.031). No evidence for an effect of aortic arch obstruction and arterial oxygen saturation on cerebral perfusion was found. After adjusting for hemodynamic and oxygen saturation parameters, deep (p = 0.018) and cortical (p = 0.012) gray matter perfusion was increased in patients with CHD compared to controls. CONCLUSION: We detected regional differences in compensation to the cerebral steal effect in patients with severe CHD. IMPACT: Patients with severe congenital heart disease (CHD) have altered postnatal brain hemodynamics. A systemic-to-pulmonary shunt was associated with decreased perfusion in cortical gray matter but preserved perfusion in deep gray matter, pointing towards regional differences in compensation to the cerebral steal effect. No effects of aortic arch obstruction and arterial oxygenation on cerebral perfusion were seen. Cerebral perfusion was increased in patients with CHD compared to healthy controls after adjusting for hemodynamic alterations and oxygen saturation. To improve neuroprotection and neurodevelopmental outcomes, it is important to increase our understanding of the factors influencing cerebral perfusion in neonates with severe CHD.

Neurometabolic changes in neonates with congenital heart defects and their relation to neurodevelopmental outcome.

BACKGROUND: Altered neurometabolite ratios in neonates undergoing cardiac surgery for congenital heart defects (CHD) may serve as a biomarker for altered brain development and neurodevelopment (ND). METHODS: We analyzed single voxel 3T PRESS H1-MRS data, acquired unilaterally in the left basal ganglia and white matter of 88 CHD neonates before and/or after neonatal cardiac surgery and 30 healthy controls. Metabolite ratios to Creatine (Cr) included glutamate (Glu/Cr), myo-Inositol (mI/Cr), glutamate and glutamine (Glx/Cr), and lactate (Lac/Cr). In addition, the developmental marker N-acetylaspartate to choline (NAA/Cho) was evaluated. All children underwent ND outcome testing using the Bayley Scales of Infant and Toddler Development Third Edition (BSID-III) at 1 year of age. RESULTS: White matter NAA/Cho ratios were lower in CHD neonates compared to healthy controls (group beta estimate: -0.26, std. error 0.07, 95% CI: -0.40 - 0.13, p value <0.001, FDR corrected p value = 0.010). We found no correlation between pre- or postoperative white matter NAA/Cho with ND outcome while controlling for socioeconomic status and CHD diagnosis. CONCLUSION: Reduced white matter NAA/Cho in CHD neonates undergoing cardiac surgery may reflect a delay in brain maturation. Further long-term MRS studies are needed to improve our understanding of the clinical impact of altered metabolites on brain development and outcome. IMPACT: NAA/Cho was reduced in the white matter, but not the gray matter of CHD neonates compared to healthy controls. No correlation to the 1-year neurodevelopmental outcome (Bayley-III) was found. While the rapid change of NAA/Cho with age might make it a sensitive marker for a delay in brain maturation, the relationship to neurodevelopmental outcome requires further investigation.

Counting on random number generation: Uncovering mild executive dysfunction in congenital heart disease.

Congenital heart disease (CHD) is associated with various neurocognitive deficits, particularly targeting executive functions (EFs), of which random number generation (RNG) is one indicator. RNG has, however, never been investigated in CHD. We administered the Mental Dice Task (MDT) to 67 young adults with CHD and 55 healthy controls. This 1-minute-task requires the generation of numbers 1 to 6 in a random sequence. RNG performance was correlated with a global EF score. Participants underwent MRI to examine structural-volumetric correlates of RNG. Compared to controls, CHD patients showed increased backward counting, reflecting deficient inhibition of automatized behavior. They also lacked a small-number bias (higher frequency of small relative to large numbers). RNG performance was associated with global EF scores in both groups. In CHD patients, MRI revealed an inverse association of counting bias with most of the volumetric measurements and the amount of small numbers was positively associated with corpus callosum volume, suggesting callosal involvement in the "pseudoneglect in number space". In conclusion, we found an impaired RNG performance in CHD patients, which is associated with brain volumetric measures. RNG, reportedly resistant to learning effects, may be an ideal task for the longitudinal assessment of EFs in patients with CHD.

Feasibility of Non-Gated Dynamic Fetal Cardiac MRI for Identification of Fetal Cardiovascular Anatomy.

INTRODUCTION: The aim of this study was to evaluate the feasibility of identifying the fetal cardiac and thoracic vascular structures with non-gated dynamic balanced steady-state free precession (SSFP) MRI sequences. METHODS: We retrospectively assessed the visibility of cardiovascular anatomy in 60 fetuses without suspicion of congenital heart defect. Non-gated dynamic balanced SSFP sequences were acquired in three anatomic planes of the fetal thorax. The images were analyzed following a segmental approach in consensus reading by an experienced pediatric cardiologist and radiologist. An imaging score was defined by giving one point to each visualized structure, yielding a maximum score of 21 points. Image quality was rated from 0 (poor) to 2 (excellent). The influence of gestational age (GA), field strength, placenta position, and maternal panniculus on image quality and imaging score were tested. RESULTS: 30 scans were performed at 1.5T, 30 at 3T. Heart position, atria, and ventricles could be seen in all 60 fetuses. Basic diagnosis (>12 points) was achieved in 54 cases. The mean imaging score was 16.8+/-3.8. Maternal panniculus (r = -0.3; p = 0.015) and GA (r = 0.6; p < 0.001) correlated with imaging score. Field strength influenced image quality, with 1.5T being better than 3T images (p = 0.012). Imaging score or quality was independent of placenta position. CONCLUSION: Fetal cardiac MRI with non-gated SSFP sequences enables recognition of basic cardiovascular anatomy.

Sleep-related and diurnal effects on brain diffusivity and cerebrospinal fluid flow.

The question of how waste products are cleared from the brain, and the role which sleep plays in this process, is critical for our understanding of a range of physical and mental illnesses. In rodents, both circadian and sleep-related processes appear to facilitate clearance of waste products. The purpose of this study was to investigate whether overnight changes in diffusivity, brain volumes, and cerebrospinal fluid flow measured with MRI are associated with sleep parameters from overnight high-density sleep EEG, and circadian markers. In healthy adults investigated with MRI before and after sleep EEG, we observed an increase in water diffusivity overnight, which was positively related to the proportion of total sleep time spent in rapid eye movement (REM) sleep, and negatively associated with the fraction of sleep time spent in non rapid eye movement (NREM) sleep. Diffusivity was also associated with the sleep midpoint, a circadian marker. CSF flow increased overnight; this increase was unrelated to sleep or diffusivity measures but was associated with circadian markers. These results provide evidence for both sleep related and diurnal effects on water compartmentalisation within the brain.

Altered brain metabolism contributes to executive function deficits in school-aged children born very preterm.

BACKGROUND: Executive function deficits in children born very preterm (VPT) have been linked to anatomical abnormalities in white matter and subcortical brain structures. This study aimed to investigate how altered brain metabolism contributes to these deficits in VPT children at school-age. METHODS: Fifty-four VPT participants aged 8-13 years and 62 term-born peers were assessed with an executive function test battery. Brain metabolites were obtained in the frontal white matter and the basal ganglia/thalami, using proton magnetic resonance spectroscopy (MRS). N-acetylaspartate (NAA)/creatine (Cr), choline (Cho)/Cr, glutamate + glutamine (Glx)/Cr, and myo-Inositol (mI)/Cr were compared between groups and associations with executive functions were explored using linear regression. RESULTS: In the frontal white matter, VPT showed lower Glx/Cr (mean difference: -5.91%, 95% CI [-10.50, -1.32]), higher Cho/Cr (7.39%, 95%-CI [2.68, 12.10]), and higher mI/Cr (5.41%, 95%-CI [0.18, 10.64]) while there were no differences in the basal ganglia/thalami. Lower executive functions were associated with lower frontal Glx/Cr ratios in both groups (ß = 0.16, p = 0.05) and higher mI/Cr ratios in the VPT group only (interaction: ß = -0.17, p = 0.02). CONCLUSION: Long-term brain metabolite alterations in the frontal white matter may be related to executive function deficits in VPT children at school-age. IMPACT: Very preterm birth is associated with long-term brain metabolite alterations in the frontal white matter. Such alterations may contribute to deficits in executive function abilities. Injury processes in the brain can persist for years after the initial insult. Our findings provide new insights beyond structural and functional imaging, which help to elucidate the processes involved in abnormal brain development following preterm birth. Ultimately, this may lead to earlier identification of children at risk for developing deficits and more effective interventions.

Left temporal plane growth predicts language development in newborns with congenital heart disease.

Congenital heart defects are the most common congenital anomalies, accounting for a third of all congenital anomaly cases. While surgical correction dramatically improved survival rates, the lag behind normal neurodevelopment appears to persist. Deficits in higher cognitive functions are particularly common, including developmental delay in communication and oral-motor apraxia. It remains unclear whether the varying degree of cognitive developmental delay is reflected in variability in brain growth patterns. To answer this question, we aimed to investigate whether the rate of regional brain growth is correlated with later life neurodevelopment. Forty-four newborns were included in our study, of whom 33 were diagnosed with dextro-transposition of the great arteries and 11 with other forms of severe congenital heart defects. During the first month of life, neonates underwent corrective or palliative cardiovascular bypass surgery, pre- and postoperative cerebral MRI were performed 18.7 ± 7.03 days apart. MRI was performed in natural sleep on a 3.0 T scanner using an 8-channel head coil, fast spin-echo T2-weighted anatomical sequences were acquired in three planes. Based on the principles of deformation-based morphometry, we calculated brain growth rate maps reflecting average daily growth occurring between pre- and postoperative brain images. An explorative, whole-brain, threshold-free cluster enhancement analysis revealed strong correlation between the growth rate of the Heschl's gyrus, anterior planum temporale and language score at 12 months of age, corrected for demographic variables (P = 0.018, t = 5.656). No significant correlation was found between brain growth rates and motor or cognitive scores. Post hoc analysis showed that the length of hospitalization interacted with this correlation, longer hospitalization resulted in faster enlargement of the internal CSF spaces. Our longitudinal cohort study provides evidence for the early importance of left-dominant perisylvian regions in auditory and language development before direct postnatal exposure to native language. In congenital heart disease patients, the perioperative period results in a critical variability of brain growth rate in this region, which is a reliable neural correlate of language development at 1 year of age.

Diurnal changes in human brain glutamate + glutamine levels in the course of development and their relationship to sleep.

Sleep slow waves during non-rapid eye movement (NREM) sleep play a crucial role in maintaining cortical plasticity, a process that is especially important in the developing brain. Children show a considerably larger overnight decrease in slow wave activity (SWA; the power in the EEG frequency band between 1 and 4.5 â€‹Hz during NREM sleep), which constitutes the primary electrophysiological marker for the restorative function of sleep. We previously demonstrated in adults that this marker correlates with the overnight reduction in cortical glutamate â€‹+ â€‹glutamine (GLX) levels assessed by magnetic resonance spectroscopy (MRS), proposing GLX as a promising biomarker for the interplay between cortical plasticity and SWA. Here, we used a multimodal imaging approach of combined MRS and high-density EEG in a cross-sectional cohort of 46 subjects from 8 to 24 years of age in order to examine age-related changes in GLX and its relation to SWA. Gray matter volume, GLX levels and SWA showed the expected age-dependent decrease. Unexpectedly, the overnight changes in GLX followed opposite directions when comparing children to adults. These age-related changes could neither be explained by the overnight decrease in SWA nor by circadian factors.

Imaging glutamate redistribution after acute N-acetylcysteine administration: A simultaneous PET/MR study.

Glutamate is the most abundant excitatory neurotransmitter in the human brain, but in vivo imaging of acute fluctuations in glutamatergic levels has not been well established. The purpose of this study was to examine acute changes in glutamate after stimulation with N-acetylcysteine (NAC) using a simultaneous positron emission tomography/magnetic resonance spectroscopy (PET/MRS) approach. Ten healthy adult males were examined in two scanning sessions, and 5g NAC was administered 1 h prior to one of the scan sessions. Simultaneous PET/MR data were acquired using an integrated 3T PET/MR scanner. Glutamate (Glu), glutamine (Gln), and glutamate + glutamine (Glx) levels were assessed from MRS data collected from the basal ganglia with PRESS and from the left prefrontal cortex with PRESS and MEGAPRESS, and mGluR5 binding (BPND) was assessed from PET data collected with [18F]PSS232. NAC administration was associated with a significant reduction in Glx and Gln in the basal ganglia spectra, and in Glx in the frontal MEGAPRESS spectra (p < 0.05); no differences in [18F]PSS232 BPND were observed with NAC, although a correlation between pre-/post-treatment Glx and baseline BPnd was found. The MRS-visible Glx signal is sensitive to acute fluctuations in glutamate. The change in Glx was mostly driven by a change in Gln, lending weight to the notion that Gln can provide a proxy marker for neurotransmitter/synaptic glutamate. [18F]PSS232 binding is not sensitive to acute glutamate shifts independently, but was associated with the extent of glutamate liberation upon NAC stimulation.

Diurnal changes in glutamate + glutamine levels of healthy young adults assessed by proton magnetic resonance spectroscopy.

The glutamatergic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor is involved in synaptic plasticity processes, and animal studies have demonstrated altered expression across the sleep wake cycle. Accordingly, glutamate levels are reduced during non-rapid eye movement (NREM) sleep and the rate of this decrease is positively correlated with sleep EEG slow wave activity (SWA). Here, we combined proton magnetic resonance spectroscopy (1 H-MRS) and high-density sleep EEG to assess if 1 H-MRS is sensitive to diurnal changes of glutamate + glutamine (GLX) in healthy young adults and if potential overnight changes of GLX are correlated to SWA. 1 H-MRS was measured in the parietal lobe in the evening and in the subsequent morning. High-density sleep EEG was recorded overnight between the evening and morning scans. Our results revealed a significant overnight reduction in GLX, but no significant changes in other metabolites. The decrease in GLX positively correlated with the decrease of SWA. Our study demonstrates that quantification of diurnal changes in GLX is possible by means of 1 H-MRS and indicates that overnight changes in GLX are related to SWA, a marker that is closely linked to the restorative function of sleep. This relationship might be of particular interest in clinical populations in which sleep is disturbed.

Microvascular perfusion of the placenta, developing fetal liver, and lungs assessed with intravoxel incoherent motion imaging.

BACKGROUND: In utero intravoxel incoherent motion magnetic resonance imaging (IVIM-MRI) provides a novel method for examining microvascular perfusion fraction and diffusion in the developing human fetus. PURPOSE: To characterize gestational changes in the microvascular perfusion fraction of the placenta, fetal liver, and lungs using IVIM-MRI. STUDY TYPE: Retrospective, cross-sectional study. SUBJECTS: Fifty-five datasets from 33 singleton pregnancies were acquired (17-36 gestational weeks). FIELD STRENGTH/SEQUENCE: In utero diffusion-weighted echo-planar imaging at 1.5T and 3.0T with b-factors ranging from 0 to 900 s/mm2 in 16 steps. ASSESSMENT: Using the IVIM principle, microvascular perfusion fraction (f), pseudodiffusion (D*), and diffusion coefficients (d) were estimated for the placenta, liver, and lungs with a biexponential model. A free-form nonlinear deformation algorithm was used to correct for the frame-by-frame motion of the fetal organs and the placenta. The IVIM parameters were then compared to a Doppler ultrasound-based assessment of the umbilical artery resistance index. STATISTICAL TESTS: Pearson product-moment correlation coefficient (PMCC) to reveal outlier corrected correlations between Doppler and IVIM parameters. Gestational age-related changes were assessed using linear regression analysis (LR). RESULTS: Placental f (0.29 ± 0.08) indicates high blood volume in the microvascular compartment, moderately increased during gestation (LR, R = 0.338), and correlated negatively with the umbilical artery resistance index (PMCC, R = -0.457). The f of the liver decreased sharply during gestation (LR, R = -0.436). Lung maturation was characterized by increasing perfusion fraction (LR, R = 0.547), and we found no gestational changes in d and D* values (LR, R = -0.013 and R = 0.051, respectively). The Doppler measurements of the umbilical artery and middle cerebral artery did not correlate with the IVIM parameters of the lungs and liver. DATA CONCLUSION: Gestational age-associated changes of the placental, liver, and lung IVIM parameters likely reflect changes in placental and fetal circulation, and characterize the trajectory of microstructural and functional maturation of the fetal vasculature. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2017.

Reduction of brain volumes after neonatal cardiopulmonary bypass surgery in single-ventricle congenital heart disease before Fontan completion.

BackgroundLittle is known about the relationship between brain volumes and neurodevelopmental outcome at 2 years of age in children with single-ventricle congenital heart disease (CHD). We hypothesized that reduced brain volumes may be associated with adverse neurodevelopmental outcome.MethodsVolumetric segmentation of cerebral magnetic resonance imaging (MRI) scans was carried out in 44 patients without genetic comorbidities and in 8 controls. Neurodevelopmental outcome was assessed with the Bayley-III scales.ResultsGray matter (GM), deep GM, white matter (WM), and cerebrospinal fluid (CSF) volumes were 611±59, 43±4.5, 277±30, and 16.4 ml, respectively (interquartile range (IQR) 13.1, 23.3 ml). Children undergoing neonatal cardiopulmonary bypass surgery showed smaller deep GM (P=0.005) and WM (P=0.021) volumes. Brain volumes were smaller in patients compared with controls (GM: P=0.017, deep GM: P=0.012, and WM: P=0.015), whereas CSF volumes were greater (P=0.014). Of all intracranial volumes, only CSF volume was associated with neurodevelopmental outcome, accounting for 21% (P=0.011) of variability in the cognitive composite score when combined with common risk factors in a multivariable analysis.ConclusionIncreased CSF volume represents a significant risk factor for neurodevelopmental impairment in children with single-ventricle CHD. Later assessments are warranted to determine the prognostic role of intracranial volumes for long-term outcome.

Sedation for magnetic resonance imaging using propofol with or without ketamine at induction in pediatrics-A prospective randomized double-blinded study.

INTRODUCTION: Deep sedation using propofol has become a standard technique in children. This double-blinded randomized clinical trial aims to compare the clinical effects of propofol-mono-sedation vs a combination of propofol and ketamine at induction and a reduced propofol infusion rate for maintenance in children undergoing diagnostic magnetic resonance imaging. METHODS: Children aged from 3 months to 10 years scheduled as outpatients for elective magnetic resonance imaging with deep sedation were included. They were randomized into 2 groups, receiving either 1 mg/kg ketamine at induction, then a propofol infusion rate of 5 mg/kg/h or a propofol infusion rate of 10 mg/kg/h without prior ketamine. Time to full recovery (modified Aldrete score = 10) was the primary outcome. Further outcomes were quality of induction, immobilization during image acquisition, recovery, postoperative nausea and vomiting, emergence delirium using the Pediatric Anesthesia Emergence Delirium scale, vital signs and adverse cardiorespiratory events. All patients and parents as well as anesthetists, imaging technicians, and postsedation personnel were blinded. Data are given as median (range). RESULTS: In total, 347 children aged 4.0 (0.25-10.9) years, weighing 15.6 (5.3-54) kg, ASA classification I, II, or III (141/188/18) were included. The ketamine-propofol group showed significantly shorter recovery times (38 (22-65) vs 54 (37-77) minutes; median difference 14 (95% CI: 8, 20) minutes; P < .001), better quality of induction, and higher blood pressure, but higher incidence of movement requiring additional sedative drugs. There were no significant differences in respiratory side effects, cardiovascular compromise, emergence delirium, or postoperative nausea and vomiting. CONCLUSION: Both sedation concepts proved to be reliable with a low incidence of side effects. Ketamine at induction with a reduced propofol infusion rate leads to faster postanesthetic recovery.

Resisting Sleep Pressure: Impact on Resting State Functional Network Connectivity.

In today's 24/7 society, sleep restriction is a common phenomenon which leads to increased levels of sleep pressure in daily life. However, the magnitude and extent of impairment of brain functioning due to increased sleep pressure is still not completely understood. Resting state network (RSN) analyses have become increasingly popular because they allow us to investigate brain activity patterns in the absence of a specific task and to identify changes under different levels of vigilance (e.g. due to increased sleep pressure). RSNs are commonly derived from BOLD fMRI signals but studies progressively also employ cerebral blood flow (CBF) signals. To investigate the impact of sleep pressure on RSNs, we examined RSNs of participants under high (19 h awake) and normal (10 h awake) sleep pressure with three imaging modalities (arterial spin labeling, BOLD, pseudo BOLD) while providing confirmation of vigilance states in most conditions. We demonstrated that CBF and pseudo BOLD signals (measured with arterial spin labeling) are suited to derive independent component analysis based RSNs. The spatial map differences of these RSNs were rather small, suggesting a strong biological substrate underlying these networks. Interestingly, increased sleep pressure, namely longer time awake, specifically changed the functional network connectivity (FNC) between RSNs. In summary, all FNCs of the default mode network with any other network or component showed increasing effects as a function of increased 'time awake'. All other FNCs became more anti-correlated with increased 'time awake'. The sensorimotor networks were the only ones who showed a within network change of FNC, namely decreased connectivity as function of 'time awake'. These specific changes of FNC could reflect both compensatory mechanisms aiming to fight sleep as well as a first reduction of consciousness while becoming drowsy. We think that the specific changes observed in functional network connectivity could imply an impairment of information transfer between the affected RSNs.

Inter-hemispheric connectivity in the fusiform gyrus supports memory consolidation for faces.

This study investigated how changes of functional connectivity over time accompany consolidation of face memories. Based on previous research, it was hypothesized that connectivity changes in networks initially active during face perception and face encoding would be associated with individual recognition memory performance. Resting-state functional connectivity was examined shortly before, shortly after and about 40 min after incidental learning of faces. Memory performance was assessed in a surprise recognition test shortly after the last resting-state session. Results reveal that memory performance-related connectivity between the left fusiform face area and other brain areas gradually changed over the course of the experiment. Specifically, the increase in connectivity with the contralateral fusiform gyrus, the hippocampus, the amygdala and the inferior frontal gyrus correlated with recognition memory performance. As the increase in connectivity in the two final resting-state sessions was associated with memory performance, the present results demonstrate that memory formation is not restricted to the incidental learning phase but continues and increases in the following 40 min. It is discussed that the delayed increase in inter-hemisphere connectivity between the left and right fusiform gyrus is an indicator for memory formation and consolidation processes.

Hippocampal volume reduction is associated with intellectual functions in adolescents with congenital heart disease.

BACKGROUND: Adolescents undergoing early cardiopulmonary bypass surgery for congenital heart disease (CHD) may demonstrate a variety of neurocognitive impairments. These impairments can affect overall intellectual functions, but also specific memory deficits, language, and executive functions. As the hippocampus is a critical structure involved in these functions, we sought to determine whether hippocampal volume was reduced in adolescents with CHD and whether altered volumes were related to functional outcome. METHODS: At a mean age of 13.8 y, 48 adolescent survivors of childhood cardiopulmonary bypass surgery for CHD and 32 healthy controls underwent neurocognitive testing and cerebral magnetic resonance imaging. Images were quantitatively analyzed using an automated regional segmentation tool (FSL-FIRST). RESULTS: Adolescents with CHD had 10% lower total hippocampal volumes compared with controls. After controlling for total brain volume, total hippocampal volume correlated with total IQ, with working memory, and verbal comprehension in CHD patients, but not in controls. CONCLUSIONS: In adolescent survivors of cardiopulmonary bypass surgery for CHD, specific brain regions such as the hippocampus may show long-term persistent alteration and correlate with intellectual deficits, particularly with verbal and memory functions.