Akila Rajagopal

Left-handedness and language lateralization in children.

This fMRI study investigated the development of language lateralization in left- and righthanded children between 5 and 18 years of age. Twenty-seven left-handed children (17 boys, 10 girls) and 54 age- and gender-matched right-handed children were included. We used functional MRI at 3T and a verb generation task to measure hemispheric language dominance based on either frontal or temporo-parietal regions of interest (ROIs) defined for the entire group and applied on an individual basis. Based on the frontal ROI, in the left-handed group, 23 participants (85%) demonstrated left-hemispheric language lateralization, 3 (11%) demonstrated symmetric activation, and 1 (4%) demonstrated right-hemispheric lateralization. In contrast, 50 (93%) of the right-handed children showed left-hemispheric lateralization and 3 (6%) demonstrated a symmetric activation pattern, while one (2%) demonstrated a right-hemispheric lateralization. The corresponding values for the temporo-parietal ROI for the left-handed children were 18 (67%) left-dominant, 6 (22%) symmetric, 3 (11%) right-dominant and for the right-handed children 49 (91%), 4 (7%), 1 (2%), respectively. Left-hemispheric language lateralization increased with age in both groups but somewhat different lateralization trajectories were observed in girls when compared to boys. The incidence of atypical language lateralization in left-handed children in this study was similar to that reported in adults. We also found similar rates of increase in left-hemispheric language lateralization with age between groups (i.e., independent of handedness) indicating the presence of similar mechanisms for language lateralization in left- and right-handed children.

Sex differences in white matter development during adolescence: A DTI study

Adolescence is a complex transitional period in human development, composing physical maturation, cognitive and social behavioral changes. The objective of this study is to investigate sex differences in white matter development and the associations between intelligence and white matter microstructure in the adolescent brain using diffusion tensor imaging (DTI) and tract-based spatial statistics (TBSS). In a cohort of 16 typically-developing adolescents aged 13 to 17 years, longitudinal DTI data were recorded from each subject at two time points that were one year apart. We used TBSS to analyze the diffusion indices including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD). Our results suggest that boys (13-18 years) continued to demonstrate white matter maturation, whereas girls appeared to reach mature levels earlier. In addition, we identified significant positive correlations between FA and full-scale intelligence quotient (IQ) in the right inferior fronto-occipital fasciculus when both sexes were looked at together. Only girls showed significant positive correlations between FA and verbal IQ in the left cortico-spinal tract and superior longitudinal fasciculus. The preliminary evidence presented in this study supports that boys and girls have different developmental trajectories in white matter microstructure.

A 10-year longitudinal fMRI study of narrative comprehension in children and adolescents.

Comprehension of spoken narratives requires coordination of multiple language skills. As such, for normal children narrative skills develop well into the school years and, during this period, are particularly vulnerable in the face of brain injury or developmental disorder. For these reasons, we sought to determine the developmental trajectory of narrative processing using longitudinal fMRI scanning. 30 healthy children between the ages of 5 and 18 enrolled at ages 5, 6, or 7, were examined annually for up to 10 years. At each fMRI session, children were presented with a set of five, 30s-long, stories containing 9, 10, or 11 sentences designed to be understood by a 5 year old child. fMRI data analysis was conducted based on a hierarchical linear model (HLM) that was modified to investigate developmental changes while accounting for missing data and controlling for factors such as age, linguistic performance and IQ. Performance testing conducted after each scan indicated well above the chance (p<0.002) comprehension performance. There was a linear increase with increasing age in bilateral superior temporal cortical activation (BAs 21 and 22) linked to narrative processing. Conversely, age-related decreases in cortical activation were observed in bilateral occipital regions, cingulate and cuneus, possibly reflecting changes in the default mode networks. The dynamic changes observed in this longitudinal fMRI study support the increasing role of bilateral BAs 21 and 22 in narrative comprehension, involving non-domain-specific integration in order to achieve final story interpretation. The presence of a continued linear development of this area throughout childhood and teenage years with no apparent plateau, indicates that full maturation of narrative processing skills has not yet occurred and that it may be delayed to early adulthood.

DTI Values in Key White Matter Tracts from Infancy through Adolescence

BACKGROUND AND PURPOSE: DTI is an advanced neuroimaging technique that allows in vivo quantification of water diffusion properties as surrogate markers of the integrity of WM microstructure. In our study, we investigated normative data from a large number of pediatric and adolescent participants to examine the developmental trends in DTI during this conspicuous WM maturation period. MATERIALS AND METHODS: DTI data in 202 healthy pediatric and adolescent participants were analyzed retrospectively. Fractional anisotropy and mean diffusivity values in the corpus callosum and internal capsule were fitted to an exponential regression model to delineate age-dependent maturational changes across the WM structures. RESULTS: The DTI metrics demonstrated characteristic exponential patterns of progression during development and conspicuous age-dependent changes in the first 36 months, with rostral WM tracts experiencing the highest slope of the exponential function. In contrast, the highest final FA and lowest MD values were detected in the splenium of the corpus callosum and the posterior limb of the internal capsule. CONCLUSIONS: Our analysis shows that the more caudal portions of the corpus callosum and internal capsule begin the maturation process earlier than the rostral regions, but the rostral regions develop at a more accelerated pace, which may suggest that rostral regions rely on development of more caudal brain regions to instigate their development. Our normative DTI can be used as a reference to study normal spatiotemporal developmental profiles in the WM and help identify abnormal WM structures in patient populations.

Correlation of diffusion tensor imaging with executive function measures after early childhood traumatic brain injury

OBJECTIVE Examine relationships of diffusion tensor imaging (DTI) fractional anisotropy (FA) to executive function (EF) and attention measures following early childhood (3-7 years) traumatic brain injury (TBI). DESIGN Exploratory correlation and comparison study. SETTING Childrens hospital outpatient facilities. PARTICIPANTS 9 children with a history of TBI (age = 7.89 ± 1.00 years; Glasgow Coma Scale (GCS) = 10.11 ± 4.68) were compared to 12 children with OI (age = 7.51 ± 0.95). All children were at least 12 months post injury at time of evaluation. MAIN OUTCOME MEASURES FA in various regions of interest (ROI), EF and attention measures. RESULTS FA values primarily in the frontal white matter tracks correlated with EF measures. Separate tasks of inhibition and switching correlated significantly with FA in bilateral frontal lobes. Tasks combining both inhibition and switching correlated significantly with FA values in the left frontal lobe. Tasks of attention negatively correlated with FA values in the right frontal white matter and the superior longitudinal fasciculus. CONCLUSIONS Associations between late measurement of FA and EF measures following early childhood TBI suggest that persistent white matter changes, especially in the frontal white matter, may provide an index of EF deficits.

Factors determining success of awake and asleep magnetic resonance imaging scans in nonsedated children.

Effective techniques that allow children to complete magnetic resonance imaging (MRI) scans without sedation are high priority for the imaging community. We used behavioral approaches to scan 64 sleeping infants and toddlers younger than 4 years, and 156 awake children aged 2.5 to 18 years, for a neuroimaging research protocol. Infants and their families participated in a desensitization protocol for several days, then scanning was performed at the childs bedtime during natural sleep. For awake young children, a behavioral protocol was used that included tangible reinforcers, exploration of the scanner environment and a brief practice session. Two scan sessions were targeted for awake children. Success rates by participant were quantified in terms of the proportion of requisite scans in each session that were successfully acquired. The average success rate in sleeping infants and toddlers was 0.461. For awake children aged 2.5 to 6 years, success rates for each session were 0.739 and 0.847. For children aged 7 years and older, success rates were over 0.900 for both the sessions. Overall, though success was lower later in a scan session for both sleeping infants and awake young children, our results demonstrate that it is feasible to collect high-quality imaging data using standard imaging sequences in infants and children without sedation.

Diffusion Tensor Imaging Properties and Neurobehavioral Outcomes in Children with Hydrocephalus

BACKGROUND AND PURPOSE: White matter structural alterations and the correlation with neuropsychological deficits in children with hydrocephalus have not been well investigated. In this prospective study, the objectives were the following: 1) to apply DTI to detect in vivo white matter alterations based on diffusion properties in children with acute hydrocephalus, 2) to quantify early neuropsychological deficits, and 3) to explore the correlation between potential neuropsychological deficits and abnormalities in functionally related white matter. MATERIALS AND METHODS: A total of 44 children, 24 with hydrocephalus and 20 controls, were enrolled in the study. DTI indices, FA, MD, AD, and RD, were evaluated in the gCC, sCC, PLIC, and ALIC. The ABAS-II was used as a broad screener of development, including conceptual, social, practical, and motor skills. The correlation between the Motor Scale and DTI indices in the PLIC was analyzed. RESULTS: DTI analyses showed that the gCC and sCC in children with hydrocephalus had lower FA and higher MD, driven by the increased RD with statistical significance (P < .05) or trend-level significance (P = .06). The PLIC and ALIC had significantly higher AD in children with hydrocephalus (P < .05). On the ABAS-II, parent ratings of general adaptive skills, conceptual skills, and motor skills were significantly lower in children with hydrocephalus (all at P < .05). The MD and RD values in the PLIC were found to have trend-level or significant correlation with the Motor Scale (P = .057, .041, respectively). CONCLUSIONS: DTI reveals alterations in the white matter structure in children with hydrocephalus with preliminary findings suggesting correlation with clinical motor deficits.

Evidence that neurovascular coupling underlying the BOLD effect increases with age during childhood

Functional MRI using blood–oxygen‐level‐dependent (BOLD) imaging has provided unprecedented insights into the maturation of the human brain. Task‐based fMRI studies have shown BOLD signal increases with age during development (ages 5–18) for many cognitive domains such as language and executive function, while functional connectivity (resting‐state) fMRI studies investigating regionally synchronous BOLD fluctuations have revealed a developing functional organization of the brain from a local into a more distributed architecture. However, interpretation of these results is confounded by the fact that the BOLD signal is directly related to blood oxygenation driven by changes in blood flow and only indirectly related to neuronal activity, and may thus be affected by changing neuronal–vascular coupling. BOLD signal and cerebral blood flow (CBF) were measured simultaneously in a cohort of 113 typically developing awake participants ages 3–18 performing a narrative comprehension task. Using a novel voxelwise wild bootstrap analysis technique, an increased ratio of BOLD signal to relative CBF signal change with age (indicative of increased neuronal–vascular coupling) was seen in the middle temporal gyri and the left inferior frontal gyrus. Additionally, evidence of decreased relative oxygen metabolism (indicative of decreased neuronal activity) with age was found in the same regions. These findings raise concern that results of developmental BOLD studies cannot be unambiguously attributed to neuronal activity. Astrocytes and astrocytic processes may significantly affect the maturing functional architecture of the brain, consistent with recent research demonstrating a key role for astrocytes in mediating increased CBF following neuronal activity and for astrocyte processes in modulating synaptic connectivity. Hum Brain Mapp, 36:1–15, 2015.

Optimized simultaneous ASL and BOLD functional imaging of the whole brain

To compare a double‐excitation combined arterial‐spin labeling/blood‐oxygenation level dependent (ASL/BOLD) functional imaging method to a double‐echo method. ASL provides a useful complement to standard BOLD functional imaging, to map effects of cerebral hemodynamics. Whole‐brain imaging is necessary to properly characterize large functional networks. A challenge of whole‐brain ASL/BOLD is that images for ASL functional contrast must be acquired before significant longitudinal relaxation of the inverted spins occurs; however, a longer echo time (TE) is required for optimal BOLD functional contrast, lengthening the acquisition time. Thus, existing combined ASL/BOLD studies have only partial‐brain coverage.

Diffusion tensor imaging of white matter injury in a rat model of infantile hydrocephalus

ObjectiveDiffusion tensor imaging (DTI) is a non-invasive MRI technique that has been used to quantify white matter (WM) abnormality in both clinical and experimental hydrocephalus (HCP). However, no DTI study has been conducted to characterize anisotropic diffusion properties in an animal model of infantile HCP. This DTI study was designed to investigate a rat model of HCP induced at postnatal day 21, a time developmentally equivalent to the human infancy.MethodsDTI data were acquired at approximately 4 weeks after the induction of HCP with kaolin injection. Using a 7 Tesla small animal MRI scanner we performed high-resolution DTI on 12 rats with HCP and 6 saline controls. Regions of interest (ROI) examined with quantitative comparisons include the genu, body, and splenium of the corpus callosum (gCC, bCC, and sCC, respectively), anterior, middle, and posterior external capsule (aEC, mEC, and pEC, respectively), internal capsule (IC), and fornix (FX). For each ROI, DTI metrics including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (Dax), and radial diffusivity (Drad) were calculated.ResultsWe found that the anisotropic diffusion properties were abnormal across multiple WM regions in the brains of the HCP rats. Statistically significant differences included: (1) decreased FA and increased MD and Drad values in the gCC and bCC; (2) increased Dax in the sCC; (3) increased FA and Dax in the aEC; (4) increased FA in the mEC; (5) increased MD and Drad in the pEC; (6) increased FA and Dax in IC; (7) increased FA in FX.ConclusionsThese preliminary results provide the first evidence of WM injury quantified by DTI in a rat model of infantile HCP. Our data showed that DTI is a sensitive tool to characterize patterns of WM abnormalities and support the notion that WM impairment is region specific in response to HCP.