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.

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.

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.

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.

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.

In vivo detection of GABA and glutamate with MEGA-PRESS: reproducibility and gender effects.

PURPOSE: To evaluate the reproducibility of γ-amino-butyric acid (GABA) and glutamate concentrations derived using three different spectral fitting methods, and to investigate gender-related differences in neurotransmitter levels. MATERIALS AND METHODS: Single voxel MEGA-edited PRESS MR spectra were acquired from a 30-mL voxel in the dorso-lateral prefrontal cortex in 14 adult volunteers (7 female) at 3 Tesla (3T). For each participant, four consecutive resting spectra were acquired within the same scanning session. Metabolite concentrations were derived using LCModel, jMRUI, and locally written peak fitting software. The within-session reproducibility for each analysis method was calculated as the average coefficient of variation (CV) of the GABA and Glx (glutamate+glutamine) concentrations. Gender differences in GABA and Glx were evaluated using a two-tailed unpaired t-test. RESULTS: LCModel provided the best reproducibility for both GABA (CV 7%) and Glx (CV 6%). GABA, Glx, and glutamate concentrations were significantly higher in the male participants, (P = 0.02, P = 0.001, and P < 0.001, respectively). CONCLUSION: GABA and glutamate can be quantified in vivo with high reproducibility (CV 6-7%) using frequency-domain spectral fitting methods like LCModel. However, the GABA and glutamate concentrations vary significantly between men and women, emphasizing the importance of gender-matching for studies investigating differences in neurotransmitter concentrations between mixed-cohort groups.

Optimal MRI methods for direct stereotactic targeting of the subthalamic nucleus and globus pallidus.

OBJECTIVE: Reliable identification of the subthalamic nucleus (STN) and globus pallidus interna (GPi) is critical for deep brain stimulation (DBS) of these structures. The purpose of this study was to compare the visibility of the STN and GPi with various MRI techniques and to assess the suitability of each technique for direct stereotactic targeting. METHODS: MR images were acquired from nine volunteers with T2- and proton density-weighted (PD-W) fast spin echo, susceptibility-weighted imaging (SWI), phase-sensitive inversion recovery and quantitative T1, T2 and T2* mapping sequences. Contrast-to-noise ratios (CNR) for the STN and GPi were calculated for all sequences. Targeting errors on SWI were evaluated on magnetic susceptibility maps. The sequences demonstrating the best conspicuity of DBS target structures (SWI and T2*) were then applied to ten patients with movement disorders, and the CNRs for these techniques were assessed. RESULTS: SWI offers the highest CNR for the STN, but standard PD-W images provide the best CNR for the pallidum. Susceptibility maps indicated that the GPi margins may be shifted slightly on SWI, although no shifts were seen for the STN. CONCLUSION: SWI may improve the visibility of the STN on pre-operative MRI, potentially improving the accuracy of direct stereotactic targeting.

Maturation of limbic regions in Asperger syndrome: a preliminary study using proton magnetic resonance spectroscopy and structural magnetic resonance imaging.

People with autistic spectrum disorders (ASD, including Asperger syndrome) may have developmental abnormalities in the amygdala-hippocampal complex (AHC). However, in vivo, age-related comparisons of both volume and neuronal integrity of the AHC have not yet been carried out in people with Asperger syndrome (AS) versus controls. We compared structure and metabolic activity of the right AHC of 22 individuals with AS and 22 healthy controls aged 10-50 years and examined the effects of age between groups. We used structural magnetic resonance imaging (sMRI) to measure the volume of the AHC, and magnetic resonance spectroscopy ((1)H-MRS) to measure concentrations of N-acetyl aspartate (NAA), creatine+phosphocreatine (Cr+PCr), myo-inositol (mI) and choline (Cho). The bulk volume of the amygdala and the hippocampus did not differ significantly between groups, but there was a significant difference in the effect of age on the hippocampus in controls. Compared with controls, young (but not older) people with AS had a significantly higher AHC concentration of NAA and a significantly higher NAA/Cr ratio. People with AS, but not controls, had a significant age-related reduction in NAA and the NAA/Cr ratio. Also, in people with AS, but not controls, there was a significant relationship between concentrations of choline and age so that choline concentrations reduced with age. We therefore suggest that people with AS have significant differences in neuronal and lipid membrane integrity and maturation of the AHC.

CT/MR image fusion in the postoperative assessment of electrodes implanted for deep brain stimulation.

BACKGROUND/AIMS: Stereotactic postoperative imaging is essential for verification of the position of electrodes implanted for deep brain stimulation (DBS). MRI offers superior visualisation of the DBS targets relative to CT, but previous adverse incidents have heightened concerns about risks of postoperative MRI. Preoperative MRI fused with postoperative CT offers an alternative method for evaluating electrode position, but before this method can be clinically applied, the image registration accuracy must be established. The purpose of this study was to quantitatively assess the accuracy of three different image registration and fusion methods. METHODS: Preoperative stereotactic MRI and postoperative stereotactic CT were acquired from 20 patients under- going DBS surgery (35 electrodes in total). The postoperative CT was registered and fused with the preoperative MRI, using three different registration algorithms. The position of each electrode tip was determined in stereotactic coordinates both in the (unfused) postoperative CT and the fused CT/MRI. The difference in tip position between the CT and fused CT/MRI was used to evaluate the registration accuracy. RESULTS: The mean error along the lateral, anteroposterior, and vertical axes was 0.5, 0.5, and 1 mm, respectively. CONCLUSIONS: CT/MRI fusion provides a safe, practical technique for postoperative identification of DBS electrodes.

Increased cerebral perfusion in adult attention deficit hyperactivity disorder is normalised by stimulant treatment: a non-invasive MRI pilot study.

The neurobiological basis for attention deficit hyperactivity disorder (ADHD) has not yet been fully established, although there is a growing body of evidence pointing to functional and structural abnormalities involving the basal ganglia, cerebellum, and regions of frontal grey matter. The purpose of this study was to investigate regional cerebral perfusion in adults with ADHD and age-matched control subjects, and to assess the perfusion response to stimulant treatment in the ADHD group using a non-invasive magnetic resonance perfusion imaging technique. Whole-brain cerebral perfusion images were acquired from nine right-handed male patients with ADHD and eleven age-matched control subjects using a continuous arterial spin labelling (CASL) technique. The ADHD group was assessed once on their normal treatment and once after withdrawing from treatment for at least one week. An automated voxel-based analysis was used to identify regions where the cerebral perfusion differed significantly between the ADHD and control groups, and where the perfusion altered significantly with stimulant treatment. Regional cerebral perfusion was increased in the ADHD group in the left caudate nucleus, frontal and parietal regions. Psychomotor stimulant treatment acted to normalise perfusion in frontal cortex and the caudate nucleus with additional decreases in parietal and parahippocampal regions. These findings highlight the potential sensitivity of non-invasive perfusion MRI techniques like CASL in the evaluation of perfusion differences due to illness and medication treatment, and provide further evidence that persistence of ADHD symptomatology into adulthood is accompanied by abnormalities in frontal and striatal brain regions.

Altered resting-state functional connectivity in children and adolescents born very preterm short title.

The formation of resting-state functional networks in infancy has been reported to be strongly impacted by very preterm birth. Studies in childhood and adolescence have largely focused on language processing networks and identified both decreased and increased functional connectivity. It is unclear, however, whether functional connectivity strength is altered globally in children and adolescents born very preterm and whether these alterations are related to the frequently occurring cognitive deficits. Here, resting-state functional MRI was assessed in a group of 32 school-aged children and adolescents born very preterm with normal intellectual and motor abilities and 39 healthy term-born peers. Functional connectivity within and between a comprehensive set of well-established resting-state networks was compared between the groups. IQ and executive function abilities were tested with standardized tasks and potential associations with connectivity strength were explored. Functional connectivity was weaker in the very preterm compared to the term-born group between the sensorimotor network and the visual and dorsal attention network, within the sensorimotor network and within the central executive network. In contrast, functional connectivity was stronger in the very preterm group between the sensorimotor network and parts of the salience and the central executive network. Little evidence was found that these alterations underlie lower IQ or poorer executive function abilities. This study provides evidence for a long-lasting impact of very preterm birth on the organization of resting-state networks. The potential consequence of these alterations for other neurodevelopmental domains than the ones investigated in the current study warrants further investigation.

Sleep EEG maps the functional neuroanatomy of executive processes in adolescents born very preterm.

Executive function deficits are among the most frequent sequela of very preterm birth but the underlying neuronal mechanisms are not fully understood. We used high-density electroencephalography (EEG) recordings during sleep to assess alterations in the functional neuroanatomy of executive processes in adolescents born very preterm. The topographical distribution of sleep slow wave activity (SWA; 1-4.5 Hz EEG power) has previously been used to map cognitive abilities and is known to reflect the intensity of the prior use of the respective neuronal networks. We assessed 38 adolescents born before 32 weeks of gestation [age at assessment: 12.9 (SD: 1.7), range: 10.6-16.7 years] and 43 term-born peers [13.1 (2.0), 10.0-16.9]. Executive function abilities were quantified with a composite score derived from a comprehensive task battery. All-night high-density EEG (128 electrodes) was recorded and SWA of the first hour of sleep was calculated. Abilities were significantly poorer in the very preterm compared to the term-group, particularly, if the tasks demands were high (p < .01). The score was positively correlated with sleep SWA in a cluster of 15 electrodes over frontal and negatively in a cluster of 14 electrodes over central brain regions after controlling for age at assessment and correcting for multiple comparisons. Within the frontal cluster, sleep SWA was higher in very preterm compared to term-born participants when controlling for executive function performance and age at assessment (p = .02). No difference in SWA between very preterm and term-born participants was found for the central cluster (p = .29). Our results demonstrate a local increase of sleep SWA over brain regions associated with executive processes in adolescents born very preterm compared to similarly performing term-born peers. Thus, sleep SWA seems to map the higher effort needed for executive function tasks in adolescents born very preterm.

Age-dependent and -independent changes in attention-deficit/hyperactivity disorder (ADHD) during spatial working memory performance.

OBJECTIVES: Attention-deficit/hyperactivity disorder (ADHD) has been associated with spatial working memory as well as frontostriatal core deficits. However, it is still unclear how the link between these frontostriatal deficits and working memory function in ADHD differs in children and adults. This study examined spatial working memory in adults and children with ADHD, focussing on identifying regions demonstrating age-invariant or age-dependent abnormalities. METHODS: We used functional magnetic resonance imaging to examine a group of 26 children and 35 adults to study load manipulated spatial working memory in patients and controls. RESULTS: In comparison to healthy controls, patients demonstrated reduced positive parietal and frontostriatal load effects, i.e., less increase in brain activity from low to high load, despite similar task performance. In addition, younger patients showed negative load effects, i.e., a decrease in brain activity from low to high load, in medial prefrontal regions. Load effect differences between ADHD and controls that differed between age groups were found predominantly in prefrontal regions. Age-invariant load effect differences occurred predominantly in frontostriatal regions. CONCLUSIONS: The age-dependent deviations support the role of prefrontal maturation and compensation in ADHD, while the age-invariant alterations observed in frontostriatal regions provide further evidence that these regions reflect a core pathophysiology in ADHD.

Very preterm adolescents show impaired performance with increasing demands in executive function tasks.

BACKGROUND: Very preterm birth is often associated with executive function deficits later in life. The transition to adolescence increases personal autonomy, independence and, in parallel, the demands placed on executive functions at home and in school. AIM: To assess the impact of increasing demands on executive function performance in very preterm children and adolescents with normal intellectual and motor functions. METHODS: Forty-one very preterm children and adolescents with normal intellectual and motor functions and 43 healthy term-born peers were assessed at a mean age of 13.0 years (SD: 1.9; range: 10.0-16.9). A comprehensive battery of performance-based executive function measures with different demand levels as well as a parent-rating questionnaire evaluating executive functions relevant for everyday life was applied. Standardized mean differences between groups of d ≥ .41 were regarded as clinically relevant. RESULTS: No group differences were found at the lowest demand levels of working memory (d=.09), planning (d=-.01), cognitive flexibility (d=-.21) and verbal fluency (d=-.14) tasks, but very preterm participants scored significantly below their term-born peers in the most demanding levels (d=-.50, -.59, -.43 and -.55, respectively). These differences were clinically relevant. Executive functions relevant for everyday life were strongly impaired in very preterm participants, e.g., global executive composite (d=-.66). CONCLUSION: Very preterm children and adolescents with normal intellectual and motor functions are at high risk for executive function deficits that may only become apparent with increasing demands, potentially leading to academic and other deficits.