Cerebral perfusion differences are linked to executive function performance in very preterm-born children and adolescents.

Children and adolescents born very preterm are at risk of cognitive impairment, particularly affecting executive functions. To date, the neural correlates of these cognitive differences are not yet fully understood, although converging evidence points to a pattern of structural and functional brain alterations, including reduced brain volumes, altered connectivity, and altered brain activation patterns. In very preterm neonates, alterations in brain perfusion have also been reported, but the extent to which these perfusion alterations persist into later childhood is not yet known. This study evaluated global and regional brain perfusion, measured with arterial spin labelling (ASL) MRI, in 26 very preterm children and adolescents and 34 term-born peers. Perfusion was compared between groups and relative to executive function (EF) scores, derived from an extensive EF battery assessing working memory, cognitive flexibility, and planning. Very preterm children and adolescents showed regions of altered perfusion, some of which were also related to EF scores. Most of these regions were located in the right hemisphere and included regions like the thalamus and hippocampus, which are known to play a role in executive functioning and can be affected by prematurity. In addition, perfusion decreased with age during adolescence and showed a significant interaction between birth status and sex, such that very preterm girls showed lower perfusion than term-born girls, but this trend was not seen in boys. Taken together, our results indicate a regionally altered perfusion in very preterm children and adolescents, with age and sex related changes during adolescence.

The longitudinal influence of tDCS on occipital GABA and glutamate/glutamine levels in episodic migraineurs.

This study investigated differences in the concentration of gamma-aminobutyric acid (GABA) and the combination of glutamine and glutamate (as GLX) in the early visual cortex of patients with episodic migraine and the influence of transcranial direct current stimulation (tDCS) on GABA and GLX. In this single-blind, sham-controlled trial, we randomly assigned patients with episodic migraine to receive daily anodal tDCS or sham stimulation. In addition, we included healthy controls. We acquired proton MR spectroscopy data of the visual cortex with 3 Tesla MRI at baseline and from migraine patients directly after the stimulation period and 4 months later. In 22 migraineurs and 25 controls, the GABA and the GLX concentrations did not differ at baseline between the groups. tDCS resulted in reduced concentrations of GABA but not GLX or the migraine frequency directly after the stimulation period, but not 4 months later. The changes in the levels of GABA in the early visual cortex of patients with episodic migraine in the interictal period suggest an effect of tDCS that allowed for subsequent changes in the migraine frequency. However, we might have missed relevant variations in the concentrations of these neurotransmitters during the follow-up period, as changes in migraine frequency appeared after the first MRI and disappeared before the second.

Postnatal cerebral hemodynamics in infants with severe congenital heart disease: a scoping review.

Patients with severe congenital heart disease (CHD) are at risk for impaired neurodevelopment. Cerebral blood supply may be diminished by congenital anomalies of cardiovascular anatomy and myocardial function. The aim of this scoping review was to summarize the current knowledge on cerebral hemodynamics in infants with severe CHD. A scoping review was performed. Five databases were searched for articles published from 01/1990 to 02/2022 containing information on cerebral hemodynamics assessed by neuroimaging methods in patients with severe CHD within their first year of life. A total of 1488 publications were identified, of which 26 were included. Half of the studies used Doppler ultrasound, and half used magnetic resonance imaging techniques. Studies focused on preoperative findings of cerebral hemodynamics, effects of surgical and conservative interventions, as well as on associations between cerebral hemodynamics and brain morphology or neurodevelopment. Cerebral perfusion was most severely affected in patients with single ventricle and other cyanotic disease. Neuroimaging methods provide a large variety of information on cerebral hemodynamics. Nevertheless, small and heterogeneous cohorts complicate this field of research. Further studies are needed to improve our understanding of the link between CHD and altered cerebral hemodynamics to optimize neuroprotection strategies. IMPACT: Postnatal cerebral hemodynamics are altered in infants with congenital heart disease (CHD) as compared to healthy controls, especially in most severe types such as single ventricle or other cyanotic CHD. Associations of these alterations with brain volume and maturation reveal their clinical relevance. Research in this area is limited due to the rarity and heterogeneity of diagnoses. Furthermore, longitudinal studies have rarely been conducted. Further effort is needed to better understand the deviation from physiological cerebral perfusion and its consequences in patients with CHD to optimize neuroprotection strategies.

Association of cerebellar volume with cognitive and motor function in adults with congenital heart disease.

INTRODUCTION: Patients with congenital heart disease (CHD) are at risk for cognitive and motor function impairments, brain injury, and smaller total brain volumes. The specific vulnerability of the cerebellum and its role in cognitive and motor functions in adults with congenital heart disease is not well defined. METHODS: Forty-three patients with CHD and 53 controls between 18 and 32 years underwent brain magnetic resonance imaging and cognitive, executive (EF), and motor function assessment. Cerebellar volumes were obtained using EasyMeasure and SUIT Toolbox. Associations between cerebellar volumes and cognitive and motor function were calculated using linear models. RESULTS: General cognitive and pure motor functions were lower in patients compared to controls (P < 0.05). Executive functions were within the normal range. While total cerebellar volumes and the anterior lobes were similar in patients and controls (P > 0.1), the posterior cerebellar lobe was smaller in patients with more complex CHD (P = 0.006). Smaller posterior cerebellar gray matter was not associated with cognitive functions. Smaller anterior cerebellar gray matter was not significantly related to motor functions (P > 0.1). CONCLUSION: In adults with CHD, cerebellar volume was largely unimpaired. Patients with more complex CHD may be vulnerable to changes in the posterior cerebellar gray matter. We found no significant contribution of cerebellar gray matter to cognitive and motor impairments. More advanced imaging techniques are necessary to clarify the contribution of the cerebellum to cognitive and motor functions.

Multimodal assessment shows misalignment of structural and functional thalamocortical connectivity in children and adolescents born very preterm.

Thalamocortical connections are altered following very preterm birth but it is unknown whether structural and functional alterations are linked and how they contribute to neurodevelopmental deficits. We used a multimodal approach in 27 very preterm and 35 term-born children and adolescents aged 10-16 years: Structural thalamocortical connectivity was quantified with two measures derived from probabilistic tractography of diffusion tensor data, namely the volume of thalamic segments with cortical connections and mean fractional anisotropy (FA) within the respective segments. High-density sleep EEG was recorded and sleep spindles were identified at each electrode. Sleep spindle density and integrated spindle activity (ISA) were calculated to quantify functional thalamocortical connectivity. In term-born participants, the volume of the global thalamic segment with cortical connections was strongly related to sleep spindles across the entire head (mean r â€‹= â€‹.53 â€‹± .10; range â€‹= â€‹0.35 to 0.78). Regionally, the volume of the thalamic segment connecting to frontal brain regions correlated with sleep spindle density in two clusters of electrodes over fronto-temporal brain regions (.42 â€‹± .06; 0.35 to 0.51 and 0.43 â€‹± .08; 0.35 to 0.62) and the volume of the thalamic segment connecting to parietal brain regions correlated with sleep spindle density over parietal brain regions (mean r â€‹= â€‹.43 â€‹± .07; 0.35 to 0.61). In very preterm participants, the volume of the thalamic segments was not associated with sleep spindles. In the very preterm group, mean FA within the global thalamic segment was negatively correlated with ISA over a cluster of frontal and temporo-occipital brain regions (mean r â€‹= â€‹-.53 â€‹± .07; -.41 to -.72). No association between mean FA and ISA was found in the term-born group. With this multimodal study protocol, we identified a potential misalignment between structural and functional thalamocortical connectivity in children and adolescents born very preterm. Eventually, this may shed further light on the neuronal mechanisms underlying neurodevelopmental sequelae of preterm birth.

Test-Retest Reliability of the Brain Metabolites GABA and Glx With JPRESS, PRESS, and MEGA-PRESS MRS Sequences in vivo at 3T.

BACKGROUND: The optimization of magnetic resonance spectroscopy (MRS) sequences allows improved diagnosis and prognosis of neurological and psychological disorders. Thus, to assess the test-retest and intersequence reliability of such MRS sequences in quantifying metabolite concentrations is of clinical relevance. PURPOSE: To evaluate the test-retest and intersequence reliability of three MRS sequences to estimate GABA and Glx = Glutamine+Glutamate concentrations in the human brain. STUDY TYPE: Prospective. SUBJECTS: Eighteen healthy participants were scanned twice (range: 1 day to 1 week between the two sessions) with identical protocols. FIELD STRENGTH/SEQUENCE: 3T using a 32-channel SENSE head coil in the PCC region; PRESS, JPRESS, and MEGA-PRESS sequences. ASSESSMENT: Metabolite concentrations were estimated using LCModel (for PRESS and MEGA-PRESS) and ProFit2 (for JPRESS). STATISTICAL TESTS: The test-retest reliability was evaluated by Wilcoxon signed-rank tests, Pearson's r correlation coefficients, intraclass-correlation coefficients (ICC), coefficients of variation (CV), and by Bland-Altman (BA) plots. The intersequence reliability was assessed with Wilcoxon signed-rank tests, Pearson's r correlation coefficients, and BA plots. RESULTS: For GABA, only the MEGA-PRESS sequence showed a moderate test-retest correlation (r = 0.54, ICC = 0.5, CV = 8.8%) and the BA plots indicated good agreement (P > 0.05) for all sequences. JPRESS provided less precise results and PRESS was insensitive to GABA. For Glx, the r and ICC values for PRESS (r = 0.87, ICC = 0.9, CV = 2.9%) and MEGA-PRESS (r = 0.70, ICC = 0.7, CV = 5.3%) reflect higher correlations, compared with JPRESS (r = 0.39, ICC = 0.4, CV = 20.1%). DATA CONCLUSION: MEGA-PRESS and JPRESS are suitable for the reliable detection of GABA, the first being more precise. The three sequences included in the study can measure Glx concentrations. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2020;51:1181-1191.

Total cerebrovascular blood flow and whole brain perfusion in children sedated using propofol with or without ketamine at induction: An investigation with 2D-Cine PC and ASL.

BACKGROUND: Multiple sedation regimes may be used to facilitate pediatric MRI scans. These regimes might affect cerebral blood flow and hemodynamics to varying degrees, particularly in children who may be vulnerable to anesthetic side effects. PURPOSE: To compare the effects of propofol monosedation solely (Pm group) vs. a combination of propofol and ketamine (KP group) on brain hemodynamics and perfusion. STUDY TYPE: Prospective double-blind randomized trial. FIELD STRENGTH/SEQUENCES: 1.5T and 3T. 2D-Cine phase contrast (2D-Cine PC) and pseudocontinuous arterial spin labeling (ASL). POPULATION: Children aged from 3 months to 10 years referred for MRI with deep sedation were randomized into either the KP or the Pm group. Perfusion images were acquired with ASL followed by single-slice 2D-Cine PC acquired between the cervical vertebra C2 and C3. ASSESSMENT: Average whole-brain perfusion (WBP ml.min-1 .100 ml-1 ) was extracted from the ASL perfusion maps and total cerebrovascular blood flow (CVF) was quantified by bilaterally summing the flow in the vertebral and the internal carotid arteries. The CVF values were converted to units of ml.min-1 .100 g-1 to calculate the tissue CVF100g (ml.min-1 .100 g-1 ). Images were assessed by a neuroradiologist and data from n = 81 (ASL) and n = 55 (PC) cases with no apparent pathology were entered into the analysis. STATISTICAL TESTS: Multivariate analysis of covariance was performed to compare drug sedation effects on WBP, CVF, and CVF100g . RESULTS: No significant difference in arterial flow was observed (P = 0.57), but the KP group showed significantly higher WBP than the Pm group, covarying for scanner and age (P = 0.003). A correlation analysis showed a significant positive correlation between mean WBP (ml.min-1 .100 g-1 ) and mean CVF100g . DATA CONCLUSION: The KP group showed higher perfusion but no significant difference in vascular flow compared with the Pm group. WBP and CVF100g correlated significantly, but ASL appeared to have more susceptibility to perfusion differences arising from the different sedation regimes. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 4 J. Magn. Reson. Imaging 2019;50:1433-1440.

Interictal Hyperperfusion in the Higher Visual Cortex in Patients With Episodic Migraine.

BACKGROUND: Migraine pathophysiology is complex and probably involves cortical and subcortical alterations. Structural and functional brain imaging studies indicate alterations in the higher order visual cortex in patients with migraine. Arterial spin labeling magnetic resonance imaging (ASL-MRI) is a non-invasive imaging method for assessing changes in cerebral blood flow (CBF) in vivo. OBJECTIVE: To examine if interictal CBF differs between patients with episodic migraine (EM) with or without aura and healthy controls (HC). METHODS: We assessed interictal CBF using 2D pseudo-continuous ASL-MRI on a 3 Tesla Philips scanner (University Hospital Zurich, Switzerland) in EM (N = 17, mean age 32.7 ± 9.9, 13 females) and HC (N = 19, mean age 31.0 ± 9.3, 11 females). RESULTS: Compared to HC, EM showed exclusively hyperperfusion in the right MT+ and Cohen's d effect size was 0.99 (HC mean CBF ± SD: 33.1 ± 5.9 mL/100 g/minutes; EM mean CBF: 40.9 ± 9.4 mL/100 g/minutes). EM with aura (N = 13, MwA) revealed hyperperfusion compared to HC in the right MT+ and superior temporal gyrus. For MT, Cohen's d effect size was 1.34 (HC mean CBF ± SD: 33.1 ± 5.9 mL/100 g/minutes; MwA mean CBF: 43.3 ± 8.6 mL/100 g/minutes). For the superior temporal gyrus, Cohen's d effect size was 1.28 (HC mean CBF ± SD: 40.1 ± 4.9 mL/100 g/minutes; MwA mean CBF: 47.4 ± 6.4 mL/100 g/minutes). In EM, anxiety was positively associated with CBF in the parietal operculum and angular gyrus. CONCLUSIONS: Our results suggest that extrastriate brain regions probably involved in cortical spreading depression are associated with CBF changes in the interictal state. We conclude that ASL-MRI is a sensitive method to identify local neuro-functional abnormalities in CBF in patients with EM in the interictal state.

Subcortical glutamate mediates the reduction of short-range functional connectivity with age in a developmental cohort.

Marked changes in brain physiology and structure take place between childhood and adulthood, including changes in functional connectivity and changes in the balance between main excitatory and inhibitory neurotransmitters glutamate (Glu) and GABA. The balance of these neurotransmitters is thought to underlie neural activity in general and functional connectivity networks in particular, but so far no studies have investigated the relationship between human development related differences in these neurotransmitters and concomitant changes in functional connectivity. GABA+/H2O and Glu/H2O levels were acquired in a group of healthy children, adolescents, and adults in a subcortical (basal ganglia) region, as well as in a frontal region in adolescents and adults. Our results showed higher GABA+/Glu with age in both the subcortical and the frontal voxel, which were differentially associated with significantly lower Glu/H2O with age in the subcortical voxel and by significantly higher GABA+/H2O with age in the frontal voxel. Using a seed-to-voxel analysis, we were further able to show that functional connectivity between the putamen (seed) and other subcortical structures was lower with age. Lower subcortical Glu/H2O with age mediated the lower connectivity in the dorsal putamen. Based on these results, and the potential role of Glu in synaptic pruning, we suggest that lower Glu mediates a reduction of local connectivity during human development.

Tract-based spatial statistics to assess the neuroprotective effect of early erythropoietin on white matter development in preterm infants.

Despite improved survival, many preterm infants undergo subsequent neurodevelopmental impairment. To date, no neuroprotective therapies have been implemented into clinical practice. Erythropoietin, a haematopoietic cytokine used for treatment of anaemia of prematurity, has been shown to have neuroprotective and neuroregenerative effects on the brain in many experimental studies. The aim of the study was to assess the effect of recombinant human erythropoietin on the microstructural development of the cerebral white matter using tract-based spatial statistics performed at term equivalent age. A randomized, double-blind placebo-controlled, prospective multicentre study applying recombinant human erythropoietin in the first 42 h after preterm birth entitled 'Does erythropoietin improve outcome in preterm infant' was conducted in Switzerland (NCT00413946). Preterm infants were given recombinant human erythropoietin (3000 IU) or an equivalent volume of placebo (NaCl 0.9%) intravenously before 3 h of age after birth, at 12-18 h and at 36-42 h after birth. High resolution diffusion tensor imaging was obtained at 3 T in 58 preterm infants with mean (standard deviation) gestational age at birth 29.75 (1.44) weeks, and at scanning at 41.1 (2.09) weeks. Imaging was performed at a single centre. Voxel-wise statistical analysis of the fractional anisotropy data was carried out using tract-based spatial statistics to test for differences in fractional anisotropy between infants treated with recombinant human erythropoietin and placebo using a general linear model, covarying for the gestational age at birth and the corrected gestational age at the time of the scan. Preterm infants treated with recombinant human erythropoietin demonstrated increased fractional anisotropy in the genu and splenium of the corpus callosum, the anterior and posterior limbs of the internal capsule, and the corticospinal tract bilaterally. Mean fractional anisotropy was significantly higher in preterm infants treated with recombinant human erythropoietin than in those treated with placebo (P < 0.001). We conclude that early recombinant human erythropoietin administration improves white matter development in preterm infants assessed by diffusion tensor imaging and tract-based spatial statistics.

Investigation of glutamine and GABA levels in patients with idiopathic generalized epilepsy using MEGAPRESS.

PURPOSE: Idiopathic generalized epilepsies (IGE) comprise a group of clinical syndromes associated with spike wave discharges, putatively linked to alterations in neurotransmission. The purpose of this study was to investigate whether patients with IGE have altered glutamine and γ-aminobutyric acid (GABA) levels indicative of altered excitatory and inhibitory neurotransmission in frontal regions. MATERIALS AND METHODS: Single-voxel MEGA-edited PRESS magnetic resonance imaging (MRI) spectra were acquired from a 30-mL voxel in the dorsolateral prefrontal cortex in 13 patients with IGE (8 female) and 16 controls (9 female) at 3T. Metabolite concentrations were derived using LCModel. Differences between groups were investigated using an unpaired t-test. RESULTS: Patients with IGE were found to have significantly higher glutamine than controls (P = 0.02). GABA levels were also elevated in patients with IGE (P = 0.03). CONCLUSION: Patients with IGE have increased frontal glutamine and GABA compared with controls. Since glutamine has been suggested to act as a surrogate for metabolically active glutamate, it may represent a marker for excitatory neurotransmission.

Current practice in the use of MEGA-PRESS spectroscopy for the detection of GABA.

There is increasing interest in the use of edited proton magnetic resonance spectroscopy for the detection of GABA in the human brain. At a recent meeting held at Cardiff University, a number of spectroscopy groups met to discuss the acquisition, analysis and interpretation of GABA-edited MR spectra. This paper aims to set out the issues discussed at this meeting, reporting areas of consensus around parameters and procedures in the field and highlighting those areas where differences remain. It is hoped that this paper can fulfill two needs, providing a summary of the current 'state-of-the-art' in the field of GABA-edited MRS at 3T using MEGA-PRESS and a basic guide to help researchers new to the field to avoid some of the pitfalls inherent in the acquisition and processing of edited MRS for GABA.

Stress Markers, Executive Functioning, and Resilience Among Early Adolescents With Complex Congenital Heart Disease.

Importance: Infants with complex congenital heart disease (cCHD) may experience prolonged and severe stress when undergoing open heart surgery. However, little is known about long-term stress and its role in neurodevelopmental impairments in this population. Objective: To investigate potential differences between early adolescents aged 10 to 15 years with cCHD and healthy controls in physiological stress markers by hair analysis, executive function (EF) performance, and resilience. Design, Setting, and Participants: This single-center, population-based case-control study was conducted at the University Children's Hospital Zurich, Switzerland. Patients with different types of cCHD who underwent cardiopulmonary bypass surgery during the first year of life and who did not have a genetic disorder were included in a prospective cohort study between 2004 and 2012. A total of 178 patients were eligible for assessment at ages 10 to 15 years. A control group of healthy term-born individuals was cross-sectionally recruited. Data assessment was between 2019 and 2021. Statistical analysis was performed from January to April 2023. Exposure: Patients with cCHD who underwent infant open heart surgery. Main Outcomes and Measures: Physiological stress markers were quantified by summing cortisol and cortisone concentrations measured with liquid chromatography with tandem mass spectrometry in a 3-centimeter hair strand. EFs were assessed with a neuropsychological test battery to produce an age-adjusted EF summary score. Resilience was assessed with a standardized self-report questionnaire. Results: The study included 100 patients with cCHD and 104 controls between 10 and 15 years of age (mean [SD] age, 13.3 [1.3] years); 110 (53.9%) were male and 94 (46.1%) were female. When adjusting for age, sex, and parental education, patients had significantly higher sums of hair cortisol and cortisone concentrations (ß, 0.28 [95% CI, 0.12 to 0.43]; P < .001) and lower EF scores (ß, -0.36 [95% CI, -0.49 to -0.23]; P < .001) than controls. There was no group difference in self-reported resilience (ß, -0.04 [95% CI, -0.23 to 0.12]; P = .63). A significant interaction effect between stress markers and EFs was found, indicating a stronger negative association in patients than controls (ß, -0.65 [95% CI, -1.15 to -0.15]; P = .01). The contrast effects were not significant in patients (ß, -0.21 [95% CI, -0.43 to -0.00]; P = .06) and controls (ß, 0.09 [95% CI, -0.11 to 0.30]; P = .38). Conclusions and Relevance: This case-control study provides evidence for altered physiological stress levels in adolescents with cCHD and an association with poorer EF. These results suggest that future studies are needed to better understand the neurobiological mechanisms and timing of alterations in the stress system and its role in neurodevelopment.

Acute effects of single-dose aripiprazole and haloperidol on resting cerebral blood flow (rCBF) in the human brain.

Antipsychotic drugs act on the dopaminergic system (first-generation antipsychotics, FGA), but some also directly affect serotonergic function (second-generation antipsychotics, SGA) in the brain. Short and long-term effects of these drugs on brain physiology remain poorly understood. Moreover, it remains unclear whether any physiological effect in the brain may be different for FGAs and SGAs. Immediate (+3.30 h) and different effects of single-dose FGA (haloperidol, 3 mg) and a SGA (aripiprazole, 10 mg) on resting cerebral blood flow (rCBF) were explored in the same 20 healthy volunteers using a pulsed continuous arterial spin labeling (pCASL) sequence (1.5T) in a placebo-controlled, repeated measures design. Both antipsychotics increased striatal rCBF but the effect was greater after haloperidol. Both decreased frontal rCBF, and opposite effects of the drugs were observed in the temporal cortex (haloperidol decreased, aripiprazole increased rCBF) and in the posterior cingulate (haloperidol increased, aripiprazole decreased rCBF). Further increases were evident in the insula, hippocampus, and anterior cingulate after both antipsychotics, in the motor cortex following haloperidol and in the occipital lobe the claustrum and the cerebellum after aripiprazole. Further decreases were observed in the parietal and occipital cortices after aripiprazole. This study suggests that early and different rCBF changes are evident following a single-dose of FGA and SGA. The effects occur in healthy volunteers, thus may be independent from any underlying pathology, and in the same regions identified as structurally and functionally altered in schizophrenia, suggesting a possible relationship between antipsychotic-induced rCBF changes and brain alterations in schizophrenia.

Arterial spin labelling MRI for assessment of cerebral perfusion in children with moyamoya disease: comparison with dynamic susceptibility contrast MRI.

INTRODUCTION: This study seeks to evaluate the diagnostic accuracy of cerebral perfusion imaging with arterial spin labelling (ASL) MR imaging in children with moyamoya disease compared to dynamic susceptibility contrast (DSC) imaging. METHODS: Ten children (7 females; age, 9.2 ± 5.4 years) with moyamoya disease underwent cerebral perfusion imaging with ASL and DSC on a 3-T MRI scanner in the same session. Cerebral perfusion images were acquired with ASL (pulsed continuous 3D ASL sequence, 32 axial slices, TR = 5.5 s, TE = 25 ms, FOV = 24 cm, matrix = 128 × 128) and DSC (gradient echo EPI sequence, 35 volumes of 28 axial slices, TR = 2,000 ms, TE = 36 ms, FOV = 24 cm, matrix = 96 × 96, 0.2 ml/kg Gd-DOTA). Cerebral blood flow maps were generated. ASL and DSC images were qualitatively assessed regarding perfusion of left and right ACA, MCA, and PCA territories by two independent readers using a 3-point-Likert scale and quantitative relative cerebral blood flow (rCBF) was calculated. Correlation between ASL and DSC for qualitative and quantitative assessment and the accuracy of ASL for the detection of reduced perfusion per territory with DSC serving as the standard of reference were calculated. RESULTS: With a good interreader agreement (κ = 0.62) qualitative perfusion assessment with ASL and DSC showed a strong and significant correlation (ρ = 0.77; p < 0.001), as did quantitative rCBF (r = 0.79; p < 0.001). ASL showed a sensitivity, specificity and accuracy of 94 %, 93 %, and 93 % for the detection of reduced perfusion per territory. CONCLUSION: In children with moyamoya disease, unenhanced ASL enables the detection of reduced perfusion per vascular territory with a good accuracy compared to contrast-enhanced DSC.

Cortical network for gaze control in humans revealed using multimodal MRI.

Functional magnetic resonance imaging (fMRI) techniques allow definition of cortical nodes that are presumed to be components of large-scale distributed brain networks involved in cognitive processes. However, very few investigations examine whether such functionally defined areas are in fact structurally connected. Here, we used combined fMRI and diffusion MRI-based tractography to define the cortical network involved in saccadic eye movement control in humans. The results of this multimodal imaging approach demonstrate white matter pathways connecting the frontal eye fields and supplementary eye fields, consistent with the known connectivity of these regions in macaque monkeys. Importantly, however, these connections appeared to be more prominent in the right hemisphere of humans. In addition, there was evidence of a dorsal frontoparietal pathway connecting the frontal eye field and the inferior parietal lobe, also right hemisphere dominant, consistent with specialization of the right hemisphere for directed attention in humans. These findings demonstrate the utility and potential of using multimodal imaging techniques to define large-scale distributed brain networks, including those that demonstrate known hemispheric asymmetries in humans.

Functional networks of working memory abilities in children with complex congenital heart disease: a sleep EEG study.

Working memory is frequently impaired in children with complex congenital heart disease (CHD), but little is known about the functional neuronal correlates. Sleep slow wave activity (SWA; 1-4.5 Hz EEG power) has previously been shown to reliably map neurofunctional networks of cognitive abilities in children with and without neurodevelopmental impairments. This study investigated whether functional networks of working memory abilities are altered in children with complex CHD using EEG recordings during sleep. Twenty-one children with complex CHD (aged 10.9 [SD: 0.3] years) and 17 typically-developing peers (10.5 [0.7] years) completed different working memory tasks and an overnight high-density sleep EEG recording (128 electrodes). The combined working memory score tended to be lower in children with complex CHD (CHD group: -0.44 [1.12], typically-developing group: 0.55 [1.24], d = 0.59, p = .06). The working memory score and sleep SWA of the first hour of deep sleep were correlated over similar brain regions in both groups: Strong positive associations were found over prefrontal and fronto-parietal brain regions - known to be part of the working memory network - and strong negative associations were found over central brain regions. Within these working memory networks, the associations between working memory abilities and sleep SWA (r between -.36 and .58, all p < .03) were not different between the two groups (no interactions, all p > .05). The current findings suggest that sleep SWA reliably maps working memory networks in children with complex CHD and that these functional networks are generally preserved in these patients.

Occipital transcranial direct current stimulation in episodic migraine patients: effect on cerebral perfusion.

Cerebral blood flow differs between migraine patients and healthy controls during attack and the interictal period. This study compares the brain perfusion of episodic migraine patients and healthy controls and investigates the influence of anodal transcranial direct current stimulation (tDCS) over the occipital cortex. We included healthy adult controls and episodic migraineurs. After a 28-day baseline period and the baseline visit, migraine patients received daily active or sham anodal tDCS over the occipital lobe for 28 days. All participants underwent a MRI scan at baseline; migraineurs were also scanned shortly after the stimulation period and about five months later. At baseline, brain perfusion of migraine patients and controls differed in several areas; among the stimulated areas, perfusion was increased in the cuneus of healthy controls. At the first visit, the active tDCS group had an increased blood flow in regions processing visual stimuli and a decreased perfusion in other areas. Perfusion did not differ at the second follow-up visit. The lower perfusion level in migraineurs in the cuneus indicates a lower preactivation level. Anodal tDCS over the occipital cortex increases perfusion of several areas shortly after the stimulation period, but not 5 months later. An increase in the cortical preactivation level could mediate the transient reduction of the migraine frequency.Trial registration: NCT03237754 (registered at clincicaltrials.gov; full date of first trial registration: 03/08/2017).

White matter microstructure and executive functions in congenital heart disease from childhood to adulthood: A pooled case-control study.

Congenital heart disease (CHD) patients are at risk for alterations in the cerebral white matter microstructure (WMM) throughout development. It is unclear whether the extent of WMM alterations changes with age, especially during adolescence when the WMM undergoes rapid maturation. We investigated differences in WMM between patients with CHD and healthy controls from childhood until early adulthood in a pooled sample of children, adolescents, and young adults. The association between WMM and EF was assessed. Patients with CHD (N=78) and controls (N=137) between 9 and 32 years of age underwent diffusion tensor imaging and an executive function test-battery. Mean fractional anisotropy (FA) was calculated for each white matter tract. Linear regression tested age and group effects (CHD vs control) and their interaction on FA. Relative Variable Importance (RI) estimated the independent contribution of tract FA, presence of CHD, CHD complexity, and parental education to the variability in EF. Mean FA was lower in patients compared to controls in almost all tracts (p between 0.057 and <0.001). WMM alterations in patients were not different depending on age (all interaction effects p>0.074). Predictors of EF were CHD group (RI=43%), parental education (RI=23%), CHD complexity (RI=10%), FA of the hippocampal cingulum (RI=6%) and FA of the corticospinal tract (RI=6%). The lack of group-FA-interactions indicates that the extent of altered FA remains similar across age. Altered FA is associated with EF impairments. CHD is a chronic disease with cerebral and neurocognitive impairments persisting into adulthood and, thus, long-term follow-up programs may improve overall outcome for this population.

Dehydration affects brain structure and function in healthy adolescents.

It was recently observed that dehydration causes shrinkage of brain tissue and an associated increase in ventricular volume. Negative effects of dehydration on cognitive performance have been shown in some but not all studies, and it has also been reported that an increased perceived effort may be required following dehydration. However, the effects of dehydration on brain function are unknown. We investigated this question using functional magnetic resonance imaging (fMRI) in 10 healthy adolescents (mean age = 16.8, five females). Each subject completed a thermal exercise protocol and nonthermal exercise control condition in a cross-over repeated measures design. Subjects lost more weight via perspiration in the thermal exercise versus the control condition (P < 0.0001), and lateral ventricle enlargement correlated with the reduction in body mass (r = 0.77, P = 0.01). Dehydration following the thermal exercise protocol led to a significantly stronger increase in fronto-parietal blood-oxygen-level-dependent (BOLD) response during an executive function task (Tower of London) than the control condition, whereas cerebral perfusion during rest was not affected. The increase in BOLD response after dehydration was not paralleled by a change in cognitive performance, suggesting an inefficient use of brain metabolic activity following dehydration. This pattern indicates that participants exerted a higher level of neuronal activity in order to achieve the same performance level. Given the limited availability of brain metabolic resources, these findings suggest that prolonged states of reduced water intake may adversely impact executive functions such as planning and visuo-spatial processing.