[show abstract][hide abstract] ABSTRACT: Autism spectrum disorder (ASD) refers to a range of neurodevelopmental conditions characterized by social communication deficits, repetitive behaviours, and restrictive interests. Impaired inhibition has been suggested to exacerbate the core symptoms of ASD. This is particularly critical during adolescence when social skills are maturing to adult levels. Using magnetoencephalography (MEG), we identified the location and timing pattern of neural activity associated with inhibition in adolescents with autism, compared to typically developing adolescents.
The MEG data from 15 adolescents with ASD and 15 age-matched controls (13 to 17 years) were collected during a go/no-go task with inverse ratios of go/no-go trials in two conditions: an inhibition condition (1:2) and a baseline condition (2:1). No-go trials from the two conditions were analyzed using beamformer source localizations from 200 ms to 400 ms post-stimulus onset. Significant activations were determined using permutation testing.
Adolescents with ASD recruited first the right middle frontal gyrus (200 to 250 ms) followed by the left postcentral gyrus (250 to 300 ms) and finally the left middle frontal and right medial frontal gyri (300 to 400 ms). Typically developing adolescents recruited first the left middle frontal gyrus (200 to 250 ms), followed by the left superior and inferior frontal gyri (250 to 300 ms), then the right middle temporal gyrus (300 to 350 ms), and finally the superior and precentral gyri and right inferior lobule (300 to 400 ms).
Adolescents with ASD showed recruitment limited largely to the frontal cortex unlike typically developing adolescents who recruited parietal and temporal regions as well. These findings support the presence of an atypical, restricted inhibitory network in adolescents with ASD compared to controls.
[show abstract][hide abstract] ABSTRACT: Adults with autism spectrum disorder (ASD) can demonstrate difficulties with inhibiting inappropriate social responses. Presently, little research has utilized socially relevant stimuli to explore the modulatory effects of emotion on cognitive control in this population. To assess neural mechanisms of inhibiting social stimuli, we presented images of happy or sad facial expressions in a Go/NoGo task to unmedicated adults with ASD and to controls during functional magnetic resonance imaging (fMRI). Groups did not differ on behavioural measures. Brain activation in response to NoGo vs. Go trials revealed differing regional patterns of activation within groups. Controls recruited brain regions involved in inhibition (dorsal- [DLPFC] and ventro-lateral prefrontal cortices [VLPFC], anterior cingulate cortex [ACC]), response suppression (parietal lobe), interoceptive awareness (insula), and also the fusiform and middle temporal gyri. Adults with ASD only recruited the VLPFC and fusiform gyrus, and weakly activated the ACC and insula. Between-group comparisons indicated that controls activated the DLPFC, while adults with ASD relied on the VLPFC and the fusiform gyrus to inhibit responses. Adults with ASD may have relied more on visual association cortex, possibly as a means of recruiting additional neural processes that could act as a compensatory mechanism.
[show abstract][hide abstract] ABSTRACT: The majority, but not all, of very preterm-born infants have difficulties with a variety of cognitive functions as children. It is critical to be able to predict as early as possible those who will have difficulties, to be able to direct appropriate interventions.
We are conducting multimodal structural and functional MRI studies in very preterm-born infants and following them with behavioural and neuroimaging assessments until 4 years of age. We are also completing structural and more complex functional imaging in school-aged very preterm-born children.
A number of MRI measures between preterm and term age correlate with outcome at 2 years of age. Functional and structural differences are also seen at school age; examples from these various studies are presented.
Structural and functional studies in preterm-born versus term-born infants and children, particularly if completed longitudinally, provide important information on the evolution of brain-behaviour correlates and can help predict outcome in this high-risk population.
[show abstract][hide abstract] ABSTRACT: The neural organization of cognitive processes, particularly hemispheric lateralization, changes throughout childhood and adolescence. Differences in the neural basis of relational memory between children and adults are not well characterized. In this study we used magnetoencephalography to observe the lateralization differences of hippocampal activation in children and adults during performance of a relational memory task, transverse patterning (TP). The TP task was paired with an elemental control task, which does not depend upon the hippocampus. We contrasted two hypotheses; the compensation hypothesis would suggest that more bilateral activation in children would lead to better TP performance, whereas the maturation hypothesis would predict that a more adult-like right-lateralized pattern of hippocampal activation would lead to better performance. Mean-centered partial least squares analysis was used to determine unique patterns of brain activation specific to each task per group, while diminishing activation that is consistent across tasks. Our findings support the maturation hypothesis that a more adult-like pattern of increased right hippocampal lateralization in children leads to superior performance on the TP task. We also found dynamic changes of lateralization throughout the time course for all three groups, suggesting that caution is needed when interpreting conclusions about brain lateralization. (JINS, 2013, 19, 1-11).
Journal of the International Neuropsychological Society 08/2013; · 2.70 Impact Factor
[show abstract][hide abstract] ABSTRACT: Resting state networks are proposed to reflect the neuronal connectivity that underlies cognitive processes. Consequently, abnormal behaviour of these networks due to disease or altered development may predict poor cognitive outcome. To understand how very preterm birth may affect the development of resting state connectivity, we followed a cohort of very preterm-born infants from birth through to 4 years of age using resting state functional MRI.
From a larger longitudinal cohort of infants born very preterm (<32 weeks gestational age), 36 at birth, 30 at term, 21 two-year and 22 four-year resting state fMRI datasets were acquired. Using seed-based connectivity analyses with seeds in the anterior cingulate cortex, posterior cingulate cortex, left and right motor-hand regions and left and right temporal lobes, we investigated local and inter-region connectivity as a function of group and age.
We found strong local connectivity during the preterm period, which matured into inter-hemispheric and preliminary default-mode network correlations by 4 years of age. This development is comparable to the resting state networks found in term-born infants of equivalent age.
The results of this study suggest that differences in developmental trajectory between preterm-born and term-born infants are small and, if present, would require a large sample from both populations to be detected.
[show abstract][hide abstract] ABSTRACT: Children born very preterm (<32wks' gestation) are at risk of white matter injury, particularly in frontostriatal pathways that mediate executive functioning. However, it is unclear whether very preterm children without evidence of neonatal brain injury manifest long-term white matter microstructural differences once they reach school age and if this is related to cognitive impairments.
Twenty school-aged children born very preterm (11 males, nine females; mean age 8y 6mo, standard error [SE] 1.68mo, range 7y 7mo-9y 6mo; gestational age range 24-30wks, mean gestational age 26.9wks, SE 0.4wk; birthweight 988g, SE 46g, range 570-1424g) without evidence of neonatal brain injury, and 20 sex- and age-matched term-born children (mean age 8y 4.8mo, SE 1.92mo; range 7y 2mo-9y-10.8mo) underwent neurodevelopmental assessment and diffusion tensor imaging.
Fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity were calculated within all white matter pathways and within frontostriatal projections. Children born preterm had decreased fractional anisotropy in the territories of the left external capsule, superior longitudinal fasciculus, uncinate fasciculus, and inferior fronto-occipital fasciculus. Measures of intelligence were negatively correlated with frontostriatal fractional anisotropy only in males born preterm.
Results indicate that very preterm-born children exhibit white matter disturbances that persist into middle childhood, with potential sex differences in the association between these white matter alterations and cognitive function.
Developmental Medicine & Child Neurology 07/2013; · 2.68 Impact Factor
[show abstract][hide abstract] ABSTRACT: Considerable development of the visual system occurs in the third trimester of life, a time when very preterm-born infants are in a neonatal intensive care unit (NICU). Their very early birth during a period of rapid and marked neurodevelopment and their clinical course makes them a very high-risk population. A range of different events impacts brain development and the visual system, leading to significant long-term visual dysfunction. Improved neuroimaging techniques provide an important window on the early brain and visual system development of these vulnerable infants. Greater understanding of the etiology of visual impairment subsequent to preterm birth and the timing of critical processes will allow early recognition and the earlier implementations of interventions. In the longer term, this will help clinicians optimize NICU practice to reduce the incidence of visual dysfunction in these children.
[show abstract][hide abstract] ABSTRACT: Infants born very preterm are high risk for acquired brain injury and disturbances in brain maturation. Although survival rates for preterm infants have increased in the last decades owing to improved neonatal intensive care, motor disabilities including cerebral palsy persist, and impairments in cognitive, language, social, and executive functions have not decreased. Evidence from neuroimaging studies exploring brain structure, function, and metabolism has indicated abnormalities in the brain development trajectory of very preterm-born infants that persist through to adulthood. In this chapter, we review neuroimaging approaches for the identification of brain injury in the preterm neonate. Advances in medical imaging and availability of specialized equipment necessary to scan infants have facilitated the feasibility of conducting longitudinal studies to provide greater understanding of early brain injury and atypical brain development and their effects on neurodevelopmental outcome. Improved understanding of the risk factors for acquired brain injury and associated factors that affect brain development in this population is setting the stage for improving the brain health of children born preterm.
Seminars in pediatric neurology 06/2013; 20(2):65-74.
[show abstract][hide abstract] ABSTRACT: Aim Children born very preterm (<32wk of gestation) are at risk of white matter injury, particularly in frontostriatal pathways that mediate executive functioning. However, it is unclear whether very preterm children without evidence of neonatal brain injury manifest long-term white matter microstructural differences once they reach school age and if this is related to cognitive impairments.
Method Forty young school-aged children, 20 born very preterm (mean age 8y 6mo, standard error [SE] 1.68mo; gestational age 26.9wk, SE 0.4wk) without evidence of neonatal brain injury and 20 sex- and age-matched term-born children (mean age 8y 4.8mo, SE 1.92mo) underwent neurodevelopmental assessment and diffusion tensor imaging.
Results Fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity were calculated within all white matter pathways and within frontostriatal projections. Children born preterm had decreased fractional anisotropy in the territories of the left external capsule, superior longitudinal fasciculus, uncinate fasciculus and inferior fronto-occipital fasciculus. Measures of intelligence were negatively correlated with frontostriatal fractional anisotropy only in males born preterm.
Interpretation Results indicate that very preterm-born children exhibit white matter disturbances that persist into middle childhood, with potential sex differences in the association between these white matter alterations and cognitive function.
Developmental Medicine & Child Neurology 05/2013; · 2.68 Impact Factor
[show abstract][hide abstract] ABSTRACT: Children with autism spectrum disorder (ASD) frequently engage in self-injurious behaviours, often in the absence of reporting pain. Previous research suggests that altered pain sensitivity and repeated exposure to noxious stimuli are associated with morphological changes in somatosensory and limbic cortices. Further evidence from postmortem studies with self-injurious adults has indicated alterations in the structure and organization of the temporal lobes; however, the effect of self-injurious behaviour on cortical development in children with ASD has not yet been determined. Thirty children and adolescents (mean age = 10.6 ± 2.5 years; range 7-15 years; 29 males) with a clinical diagnosis of ASD and 30 typically developing children (N = 30, mean age = 10.7 ± 2.5 years; range 7-15 years, 26 males) underwent T1-weighted magnetic resonance and diffusion tensor imaging. No between-group differences were seen in cerebral volume, surface area or cortical thickness. Within the ASD group, self-injury scores negatively correlated with thickness in the right superior parietal lobule t = 6.3, p < 0.0001, bilateral primary somatosensory cortices (SI) (right: t = 4.4, p = 0.02; left: t = 4.48, p = 0.004) and the volume of the left ventroposterior (VP) nucleus of the thalamus (r = -0.52, p = 0.008). Based on these findings, we performed an atlas-based region-of-interest diffusion tensor imaging analysis between SI and the VP nucleus and found that children who engaged in self-injury had significantly lower fractional anisotropy (r = -0.4, p = 0.04) and higher mean diffusivity (r = 0.5, p = 0.03) values in the territory of the left posterior limb of the internal capsule. Additionally, greater incidence of self-injury was associated with increased radial diffusivity values in bilateral posterior limbs of the internal capsule (left: r = 0.5, p = 0.02; right: r = 0.5, p = 0.009) and corona radiata (left: r = 0.6, p = 0.005; right: r = 0.5, p = 0.009). Results indicate that self-injury is related to alterations in somatosensory cortical and subcortical regions and their supporting white-matter pathways. Findings could reflect use-dependent plasticity in the somatosensory system or disrupted brain development that could serve as a risk marker for self-injury.
Brain Structure and Function 05/2013; · 7.84 Impact Factor
[show abstract][hide abstract] ABSTRACT: The majority of neuroimaging studies focus on brain activity during performance of cognitive tasks; however, some studies focus on brain areas that activate in the absence of a task. Despite the surge of research comparing these contrasted areas of brain function, their interrelation is not well understood. We systematically manipulated cognitive load in a working memory task to examine concurrently the relation between activity elicited by the task versus activity during control conditions. We presented adults with six levels of task demand, and compared those with three conditions without a task. Using whole-brain analysis, we found positive linear relations between cortical activity and task difficulty in areas including middle frontal gyrus and dorsal cingulate; negative linear relations were found in medial frontal gyrus and posterior cingulate. These findings demonstrated balancing of activation patterns between two mental processes, which were both modulated by task difficulty. Frontal areas followed a graded pattern more closely than other regions. These data also showed that working memory has limited capacity in adults: an upper bound of seven items and a lower bound of four items. Overall, working memory and default-mode processes, when studied concurrently, reveal mutually competing activation patterns.
[show abstract][hide abstract] ABSTRACT: Evidence from electrophysiological and functional neuroimaging studies has suggested strong lateralisation of affective processing within the insular cortices; however, little is known about the spatial location of these processes in these regions. Using quantitative meta-analytic methods the laterality of: (1) emotional processing; (2) stimulus valence (positive vs. negative); (3) perception vs. experience of emotion; and (4) sex-differences were assessed using the data from 143 functional magnetic resonance imaging studies. Activation in response to all emotional stimuli occurred in bilateral anterior and mid-insula, and the left posterior insula. Positive emotional stimuli were associated with activation in the left anterior and mid-insula, while negative emotional stimuli activated bilateral anterior and mid-insula. Activation in response to the perception and experience of emotions was highest in bilateral anterior insula, and within the mid and posterior insula it was left lateralized. In males, emotional stimuli predominantly activated the left anterior/mid-insula and right posterior insula, whereas females activated bilateral anterior insula and the left mid and posterior insula. Spatial distinctions observed in emotional processing and its subcategories can provide a comprehensive account of the role of the insular cortices in affect processing, which could aid in understanding deficits seen in psychiatric or developmental disorders.
[show abstract][hide abstract] ABSTRACT: Background:Magnetic resonance spectroscopy allows forthe non-invasive study of brain metabolism, and therefore may provide useful information about brain injuries. We examined the associationsof brain metabolite ratios in very preterm infants with white matter lesions and overall health status at birth.Methods:Spectroscopy data were obtained from 99 very preterm infants (born ≤ 32 weeks gestation) imaged shortly after birth, and from67 of these at term-equivalent age. These data were processed using LCModel. Multiple regression was used to examine the association of metabolite ratios with focal non-cystic white matter lesions visible on conventional MRI and at-birth illness severity scores.Results:Within two weeks of birth, the ratio (N-acetylaspartate + N-acetylaspartylglutamate)/(creatine + phosphocreatine) was significantly lower in those infants showing white matter abnormalities on conventional MRI. Increased lactate/(creatine + phosphocreatine) and lactate/(glycerophosphocholine + phosphocholine) were significantly associated with increasing severity of Clinical Risk Index for BabiesII (CRIB) and Apgar scores taken at 1 and 5 minutes after birth.Conclusions:Both overall health status at birth and white matter injury in preterm neonates are reflected in metabolite ratios measured shortly after birth. Long-term follow up will provide additional insight into the prognostic value of these measures.Pediatric Research (2013); doi:10.1038/pr.2013.62.
[show abstract][hide abstract] ABSTRACT: We investigated developmental differences in the cortical attention processing network using magnetoencephalography (MEG) and a spatial cueing task in 7-8 and 12-13 year old children. The cueing paradigm consisted of a centrally presented face with left or right averted eye-gaze in the gaze cue condition, and a central face with straight gaze presented with a cue stimulus to the left or right of the face in the peripheral cue condition. Cue congruency was 50 %. MEG was recorded during the two conditions and event-related beamforming was used to determine the timing and location of the brain activity related to target detection with the two types of cueing. The MEG data showed no age differences in the eye-gaze condition, but a developmental difference characterised by slower and more diffuse activations for peripheral cues in the younger versus the older age group. In the 7-8 year olds activation peaked around 300 ms, and was localised to left inferior frontal gyrus as well as posterior areas related to visuo-spatial processing. The 12-13 year olds showed a temporoparietal pattern of activation characteristic of spatial reorientation which resembled that seen for adult participants using the same paradigm (Nagata et al. 2012). The activation peaked around 200 ms and was localised to the left superior frontal gyrus, middle frontal gyrus but bilaterally near the temporoparietal junction. The data indicate maturational changes in brain activity for peripheral cueing.
[show abstract][hide abstract] ABSTRACT: Several brain regions show structural and functional abnormalities in individuals with autism spectrum disorders (ASD), but the developmental trajectory of abnormalities in these structures and how they may relate to social and communicative impairments are still unclear. We assessed the effects of age on cortical thickness in individuals with ASD, between the ages of 7 and 39 years in comparison to typically developing controls. Additionally, we examined differences in cortical thickness in relation to symptomatology in the ASD group, and their association with age. Analyses were conducted using a general linear model, controlling for sex. Social and communication scores from the Autism Diagnostic Interview-Revised (ADI-R) were correlated with the thickness of regions implicated in those functions. Controls showed widespread cortical thinning relative to the ASD group. Within regions-of-interest, increased thickness in the rostral anterior cingulate cortex was associated with poorer social scores. Additionally, a significant interaction between age and social impairment was found in the orbitofrontal cortex, with more impaired younger children having decreased thickness in this region. These results suggest that differential neurodevelopmental trajectories are present in individuals with ASD and some differences are associated with diagnostic behaviours.
Research in Autism Spectrum Disorders 01/2013; 7(1):141-150. · 2.96 Impact Factor
[show abstract][hide abstract] ABSTRACT: Autism spectrum disorder (ASD) is a characterized by deficits in social cognition and executive function. An area of particular difficulty for children with ASD is cognitive flexibility, such as the ability to shift between attentional or response sets. The biological basis of such deficits remains poorly understood, although atypical development of structural and functional brain connectivity have been reported in ASD, suggesting that disruptions of normal patterns of inter-regional communication may contribute to cognitive problems in this group. The present magnetoencephalography study measured inter-regional phase synchronization while children with ASD and typically developing matched controls (6-14 years of age) performed a set-shifting task. Reduced theta-band phase synchronization was observed in children with ASD during extradimensional set-shifting. This reduction in task-dependent inter-regional connectivity encompassed numerous areas including multiple frontal lobe regions, and indicates that problems with communication among brain areas may contribute to difficulties with executive function in ASD.
Frontiers in Human Neuroscience 01/2013; 7:785. · 2.91 Impact Factor
[show abstract][hide abstract] ABSTRACT: Magnetization transfer ratio (MTR), diffusion tensor imaging (DTI) parameters and T(1) relaxometry values were used to create parametric maps characterizing the tissue microstructure of the neonatal brain in infants born very premature (24-32 gestational weeks) and scanned at preterm and term equivalent age. Group-wise image registration was used to determine anatomical correspondence between individual scans and the pooled parametric data at the preterm and term ages. These parametric maps showed distinct contrasts whose interrelations varied across brain regions and between the preterm and term period. Discrete patterns of regional variation were observed for the different quantitative parameters, providing evidence that MRI is sensitive to multiple independent aspects of brain maturation. MTR values showed a marked change in the pattern of regional variation at term equivalent age compared to the preterm period such that the ordinal ranking of regions by signal contrast changed. This was unlike all other parameters where the regional ranking was preserved at the two time points. Interpreting the data in terms of myelination and structural organization, we report on the concordance with available histological data and demonstrate the value of quantitative MRI for tracking brain maturation over the neonatal period.
[show abstract][hide abstract] ABSTRACT: Functional activity in the anterior cingulate cortex and insula has been reported to be abnormal during social tasks in autism spectrum disorders. However, few studies have examined surface morphometry in these regions and how this may be related to autism spectrum disorder symptomatology. In this study, 27 individuals with autism spectrum disorders and 25 controls between the ages of 7 to 39 years underwent structural magnetic resonance imaging. Our primary analysis examined differences in surface area in the cingulate and insula, between individuals with and without autism spectrum disorders, as well as age-related changes and associations with social impairments. Surface area in the right cingulate was significantly different between groups and decreased more rapidly with age in autism spectrum disorder participants. In addition, greater surface area in the insula and isthmus was associated with poorer social behaviors. Results suggest atypical surface morphometry in brain regions involved in social function, which appeared to be related to poorer social ability scores.
Journal of child neurology 07/2012; · 1.59 Impact Factor
[show abstract][hide abstract] ABSTRACT: The modulation of control processes by stimulus salience, as well as associated neural activation, changes over development. We investigated age-related differences in the influence of facial emotion on brain activation when an action had to be withheld, focusing on a developmental period characterized by rapid social-emotional and cognitive change. Groups of kindergarten and young school-aged children and a group of young adults performed a modified Go/Nogo task. Response cues were preceded by happy or angry faces. After controlling for task performance, left orbitofrontal regions discriminated trials with happy vs. angry faces in children but not in adults when a response was withheld, and this effect decreased parametrically with age group. Age-related changes in prefrontal responsiveness to facial expression were not observed when an action was required, nor did this region show age-related activation changes with the demand to withhold a response in general. Such results reveal age-related differences in prefrontal activation that are specific to stimulus valence and depend on the action required.
[show abstract][hide abstract] ABSTRACT: The aim of this study was to determine the feasibility of undertaking visual functional magnetic resonance imaging (fMRI) in very preterm children.
Forty-seven infants born at less than 32 weeks gestational age (25 males, 22 females; mean (SD) age at birth 28.8 wks [1.9]) were scanned using 1.5 T MRI as part of a longitudinal neuroimaging study. These infants were scanned at preterm age (within 2 wks of birth) and at term-equivalent age. Quantitative T2* data and fMRI in response to visual stimuli (flashing strobe) were acquired in this population. T2* values were compared at preterm age and at term-equivalent age using a two-tailed t-test. A general linear model was used to evaluate occipital lobe response to visual stimuli.
T2* values were significantly higher at preterm age than at term-equivalent age in both the medial and lateral occipital lobes (preterm infants: 187.2 ms and 198.4 ms respectively; term infants: 110.9 ms and 133.2 ms respectively; p<0.002). Significant positive occipital lobe activation (q<0.01) was found in 3 out of 65 (5%) fMRIs carried out at preterm age and in 19 out of 26 (73%) scans carried out at term-equivalent age.
Visual stimuli do not elicit a reliable blood oxygen level-dependent (BOLD) response in very preterm infants during the preterm period. This suggests that BOLD fMRI may not be the appropriate modality for investigating occipital lobe function in very preterm infants.