A protocol for the analysis of DTI data collected from young children.

Analysis of scalar maps obtained by diffusion tensor imaging (DTI) produce valuable information about the microstructure of the brain white matter. The DTI scanning of child populations, compared with adult groups, requires specifically designed data acquisition protocols that take into consideration the trade-off between the scanning time, diffusion strength, number of diffusion directions, and the applied analysis techniques. Furthermore, inadequate normalization of DTI images and non-robust tensor reconstruction have profound effects on data analyses and may produce biased statistical results. Here, we present an acquisition sequence that was specifically designed for pediatric populations, and describe the analysis steps of the DTI data collected from extremely preterm-born young school-aged children and their age- and gender-matched controls. The protocol utilizes multiple software packages to address the effects of artifacts and to produce robust tensor estimation. The computation of a population-specific template and the nonlinear registration of tensorial images with this template were implemented to improve alignment of brain images from the children.

Altered working memory-related brain responses and white matter microstructure in extremely preterm-born children at school age.

Preterm birth poses a risk for neurocognitive and behavioral development. Preterm children, who have not been diagnosed with neurological or cognitive deficits, enter normal schools and are expected to succeed as their term-born peers. Here we tested the hypotheses that despite an uneventful development after preterm birth, these children might exhibit subtle abnormalities in brain function and white-matter microstructure at school-age. We recruited 7.5-year-old children born extremely prematurely (<28 weeks' gestation), and age- and gender-matched term-born controls (≥37 weeks' gestation). We applied fMRI during working-memory (WM) tasks, and investigated white-matter microstructure with diffusion tensor imaging. Compared with controls, preterm-born children performed WM tasks less accurately, had reduced activation in several right prefrontal areas, and weaker deactivation of right temporal lobe areas. The weaker prefrontal activation correlated with poorer WM performance. Preterm-born children had higher fractional anisotropy (FA) and lower diffusivity than controls in several white-matter areas, and in the posterior cerebellum, the higher FA associated with poorer visuospatial test scores. In controls, higher FA and lower diffusivity correlated with faster WM performance. Together these findings demonstrate weaker WM-related brain activations and altered white matter microstructure in children born extremely preterm, who had normal global cognitive ability.

Functional connectivity of intrinsic cognitive networks during resting state and task performance in preadolescent children.

Earlier studies on adults have shown that functional connectivity (FC) of brain networks can vary depending on the brain state and cognitive challenge. Network connectivity has been investigated quite extensively in children in resting state, much less during tasks and is largely unexplored between these brain states. Here we used functional magnetic resonance imaging and independent component analysis to investigate the functional architecture of large-scale brain networks in 16 children (aged 7-11 years, 11 males) and 16 young adults (aged 22-29 years, 10 males) during resting state and visual working memory tasks. We identified the major neurocognitive intrinsic connectivity networks (ICNs) in both groups. Children had stronger FC than adults within the cingulo-opercular network in resting state, during task performance, and after controlling for performance differences. During tasks, children had stronger FC than adults also within the default mode (DMN) and right frontoparietal (rFPN) networks, and between the anterior DMN and the frontopolar network, whereas adults had stronger coupling between the anterior DMN and rFPN. Furthermore, children compared to adults modulated the FC strength regarding the rFPN differently between the brain states. The FC within the anterior DMN correlated with age and performance in children so that the younger they were, the stronger was the FC, and the stronger the FC within this network, the slower they performed the tasks. The group differences in the network connectivity reported here, and the observed correlations with task performance, provide insight into the normative development of the preadolescent brain and link maturation of functional connectivity with improving cognitive performance.

Attention and Working Memory in Adolescents with Autism Spectrum Disorder: A Functional MRI Study.

The present study examined attention and memory load-dependent differences in the brain activation and deactivation patterns between adolescents with autism spectrum disorders (ASDs) and typically developing (TD) controls using functional magnetic resonance imaging. Attentional (0-back) and working memory (WM; 2-back) processing and load differences (0 vs. 2-back) were analysed. WM-related areas activated and default mode network deactivated normally in ASDs as a function of task load. ASDs performed the attentional 0-back task similarly to TD controls but showed increased deactivation in cerebellum and right temporal cortical areas and weaker activation in other cerebellar areas. Increasing task load resulted in multiple responses in ASDs compared to TD and in inadequate modulation of brain activity in right insula, primary somatosensory, motor and auditory cortices. The changes during attentional task may reflect compensatory mechanisms enabling normal behavioral performance. The inadequate memory load-dependent modulation of activity suggests diminished compensatory potential in ASD.

Brain activity during divided and selective attention to auditory and visual sentence comprehension tasks.

Using functional magnetic resonance imaging (fMRI), we measured brain activity of human participants while they performed a sentence congruence judgment task in either the visual or auditory modality separately, or in both modalities simultaneously. Significant performance decrements were observed when attention was divided between the two modalities compared with when one modality was selectively attended. Compared with selective attention (i.e., single tasking), divided attention (i.e., dual-tasking) did not recruit additional cortical regions, but resulted in increased activity in medial and lateral frontal regions which were also activated by the component tasks when performed separately. Areas involved in semantic language processing were revealed predominantly in the left lateral prefrontal cortex by contrasting incongruent with congruent sentences. These areas also showed significant activity increases during divided attention in relation to selective attention. In the sensory cortices, no crossmodal inhibition was observed during divided attention when compared with selective attention to one modality. Our results suggest that the observed performance decrements during dual-tasking are due to interference of the two tasks because they utilize the same part of the cortex. Moreover, semantic dual-tasking did not appear to recruit additional brain areas in comparison with single tasking, and no crossmodal inhibition was observed during intermodal divided attention.

Visuospatial working memory in 7- to 12-year-old children with disruptive behavior disorders.

Very little evidence exists on working memory (WM) deficits in children with disruptive behavior disorders such as Oppositional Defiant Disorder (ODD) or Conduct Disorder (CD). We evaluated the function of visuospatial WM in patients (n = 26) with ODD/CD compared with age- and gender-matched controls (n = 26) while controlling for the comorbid diagnosis of Attention-Deficit/Hyperactivity-Disorder (ADHD) in patients. The patients were diagnosed by Kiddie-SADS-PL interview, psychiatric symptoms were measured using Child Behavior Checklist and Teacher Report Form. WM was measured by computer-based visuospatial n-back tasks with three difficulty levels. Incorrect responses (reflecting WM performance) in all WM tasks were significantly higher in patients with ODD/CD than in controls. Both patient subgroups, ODD/CD + ADHD and ODD/CD alone, had WM deficits compared with controls. These results suggest that children with ODD/CD have visuospatial WM deficits that are not accounted for by comorbid ADHD.

Responsiveness and functional connectivity of the scene-sensitive retrosplenial complex in 7-11-year-old children.

Brain imaging studies have identified two cortical areas, the parahippocampal place area (PPA) and the retrosplenial complex (RSC), that respond preferentially to the viewing of scenes. Contrary to the PPA, little is known about the functional maturation and cognitive control of the RSC. Here we used functional magnetic resonance imaging and tasks that required attention to scene (or face) images and suppression of face (or scene) images, respectively, to investigate task-dependent modulation of activity in the RSC and whole-brain functional connectivity (FC) of this area in 7-11-year-old children and young adults. We compared responsiveness of the RSC with that of the PPA. The RSC was selectively activated by scene images in both groups, albeit less than the PPA. Children modulated activity between the tasks similarly in the RSC and PPA, and to the same extent as adults in PPA, whereas adults modulated activity in the RSC less than in PPA. In children, the whole brain FC of the RSC was stronger in the Sf than Fs task between the left RSC and right fusiform gyrus. The between groups comparison suggested stronger FC in children than adults in the Sf task between the right RSC and the left inferior parietal lobule and intraparietal sulcus. Together the results suggest that the function of the RSC and the related networks undergo dynamic changes over the development from 7-11-year-old children to adulthood.

Regulation of brain activity in the fusiform face and parahippocampal place areas in 7-11-year-old children.

Developmental studies have demonstrated that cognitive processes such as attention, suppression of interference and memory develop throughout childhood and adolescence. However, little is currently known about the development of top-down control mechanisms and their influence on cognitive performance. In the present study, we used functional magnetic resonance imaging to investigate modulation of activity in the ventral visual cortex in healthy 7-11-year-old children and young adults. The participants performed tasks that required attention to either face (Fs task) or scene (Sf task) images while trying to ignore distracting scene or face images, respectively. A face-selective area in the fusiform gyrus (fusiform face area, FFA) and an area responding preferentially to scene images in the parahippocampal gyrus (parahippocampal place area, PPA) were defined using functional localizers. Children responded slower and less accurately in the tasks than adults. In children, the right FFA was less selective to face images and regulation of activity between the Fs and Sf tasks was weaker compared to adults. In the PPA, selectivity to scenes and regulation of activity, there according to the task demands were comparable between children and adults. During the tasks, children activated prefrontal cortical areas including the middle (MFG) and superior (SFG) frontal gyrus more than adults. Functional connectivity between the right FFA and left MFG was stronger in adults than children in the Fs task. Children, on the other hand, had stronger functional connectivity than adults in the Sf task between the right FFA and right PPA and between right MFG and medial SFG. There were no group differences in the functional connectivity between the PPA and the prefrontal cortex (PFC). Together the results suggest that, in 7-11-year-old children, the FFA is still immature, whereas the selectivity to scenes and regulation of activity in the PPA is comparable to adults. The results also indicated functional immaturity of the PFC in children compared to adults and weaker connectivity between the PFC and the rFFA, explaining the weaker regulation of activity in the rFFA between the Fs and Sf tasks.

Working memory, attention, inhibition, and their relation to adaptive functioning and behavioral/emotional symptoms in school-aged children.

The present study investigated the development of executive functions (EFs) and their associations with performance and behavior at school in 8-12-year-old children. The EFs were measured by computer-based n-back, Continuous Performance and Go/Nogo tasks. School performance was evaluated by Teacher Report Form (TRF) and behavior by TRF and Child Behavior Checklist. The studied dimensions of EF were cognitive efficiency/speed, working memory/attention and inhibitory control. Strong age effects were found for these cognitive abilities (p values <0.01). Inhibitory control was associated with better adaptive functioning (learning, working hard and behaving well), academic performance and less psychiatric symptoms (p values <0.05), specially in 8-9-year-old children. In this youngest age group low inhibitory control was also associated with teacher-reported inattention (p = 0.042). Low inhibitory control was associated with teacher- and parent-reported internalizing symptoms (p < 0.01). These results suggest that maturational factors may underlie low adaptive functioning and psychiatric symptoms during early school years. Further studies are needed to evaluate the association between inhibition and emotional symptoms.

Brain activation and deactivation during location and color working memory tasks in 11-13-year-old children.

Using functional magnetic resonance imaging (fMRI) and n-back tasks we investigated whether, in 11-13-year-old children, spatial (location) and nonspatial (color) information is differentially processed during visual attention (0-back) and working memory (WM) (2-back) tasks and whether such cognitive task performance, compared to a resting state, results in regional deactivation. The location 0-back task, compared to the color 0-back task, activated segregated areas in the frontal, parietal and occipital cortices whereas no differentially activated voxels were obtained when location and color 2-back tasks were directly contrasted. Several midline cortical areas were less active during 0- and 2-back task performance than resting state. The task-induced deactivation increased with task difficulty as demonstrated by larger deactivation during 2-back than 0-back tasks. The results suggest that, in 11-13-year-old children, the visual attentional network is differently recruited by spatial and nonspatial information processing, but the functional organization of cortical activation in WM in this age group is not based on the type of information processed. Furthermore, 11-13-year-old children exhibited a similar pattern of cortical deactivation that has been reported in adults during cognitive task performance compared to a resting state.

Processing of auditory and visual location information in the monkey prefrontal cortex.

Visuospatial working memory mechanisms have been studied extensively at single cell level in the dorsolateral prefrontal cortex (PFCd) in nonhuman primates. Despite the importance of short-term memory of sound location for behavioral orientation, there are only a few studies on auditory spatial working memory. The purpose of this study was to investigate neuronal mechanisms underlying working memory processing of auditory and visual location information at single cell level in the PFCd. Neuronal activity was recorded in monkeys performing a delayed matching-to-sample task (DMTS). The location of a visual or auditory stimulus was used as a memorandum. The majority of the neurons that were activated during presentation of the cue memorandum were selective either for visual or auditory spatial information. A small group of cue related bimodal neurons were sensitive to the location of the cue regardless of whether the stimulus was visual or auditory, suggesting modality independent processing of spatial information at cellular level in the PFCd. Most neurons that were activated during the delay period were modality specific, responding either during visual or auditory trials. All bimodal delay related neurons that responded during both visual and auditory trials were spatially nonselective. The results of the present study suggest that in addition to the modality specific parallel mechanism, working memory of auditory and visual space also involves modality independent processing at cellular level in the PFCd.

Audiospatial and visuospatial working memory in 6-13 year old school children.

The neural processes subserving working memory, and brain structures underlying this system, continue to develop during childhood. We investigated the effects of age and gender on audiospatial and visuospatial working memory in a nonclinical sample of school-aged children using n-back tasks. The results showed that auditory and visual working memory performance improves with age, suggesting functional maturation of underlying cognitive processes and brain areas. The gender differences found in the performance of working memory tasks suggest a larger degree of immaturity in boys than girls at the age period of 6-10 yr. The differences observed between the mastering of auditory and visual working memory tasks may indicate that visual working memory reaches functional maturity earlier than the corresponding auditory system.

Working memory and sleep in 6- to 13-year-old schoolchildren.

OBJECTIVE: To study the associations between sleep quality/quantity and performance in auditory/visual working memory tasks of different load levels. METHOD: Sixty schoolchildren aged 6 to 13 years from normal school classes voluntarily participated. Actigraphy measurement was done during a typical school week for 72 consecutive hours. It was timed together with the working memory experiments to obtain information on children's sleep during that period. The n-back task paradigm was used to examine auditory and visual working memory functions. RESULTS: Lower sleep efficiency and longer sleep latency were associated with a higher percentage of incorrect responses in working memory tasks at all memory load levels (partial correlations, controlling for age, all p values < .05, except in visual 0-back and auditive 2-back tasks); shorter sleep duration was associated with performing tasks at the highest load level only (partial correlations, controlling for age,p < .05). Also in general linear models (controlling for age, gender, and socioeconomic status), sleep efficiency (F = 11.706, p = .050) and latency (F = 3.588, p = .034) were significantly associated with the mean incorrect response rate in auditory working memory tasks. CONCLUSIONS: Sleep quality and quantity affect performance of working memory tasks in school-age children. In children with learning difficulties the possibility of underlying sleep problems should be excluded.