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Biomedical subjects

Sarah Durston

Publications and source records attributed to Sarah Durston.

14 recordsLinked to original sources

Caudate nucleus is enlarged in high-functioning medication-naive subjects with autism.

BACKGROUND: Autism is defined by three symptom clusters, including repetitive and stereotyped behavior. Previous studies have implicated basal ganglia in these behaviors. Earlier studies investigating basal ganglia in autism have included subjects on neuroleptics known to affect basal ganglia volumes. Therefore, we investigated these structures in medication-naive subjects with autism. METHODS: Volumetric magnetic resonance measures of caudate, putamen, and nucleus accumbens were compared in two independent samples of medication-naive, high-functioning subjects with autism or Asperger syndrome: 1) 21 affected children and adolescents and 21 matched control subjects; and 2) 21 affected adolescents and young adults and 21 matched control subjects. RESULTS: Caudate nucleus was enlarged in both samples. This result remained significant after correction for total brain volume. CONCLUSIONS: These results implicate caudate nucleus in autism, as an enlargement of this structure was disproportional to an increase in total brain volume in two independent samples of medication-naive subjects with autism.

Adolescent↗

Activation in ventral prefrontal cortex is sensitive to genetic vulnerability for attention-deficit hyperactivity disorder.

BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) is a heritable neuropsychiatric disorder, associated with atypical patterns of brain activation in functional imaging studies. Neuroimaging measures may serve as an intermediate phenotype in genetic studies of ADHD, as they are putatively more closely linked to gene expression than a clinical diagnosis. METHODS: We used rapid, mixed-trial, event-related functional magnetic resonance imaging (fMRI) to investigate changes in brain activation during a go no-go task in boys with ADHD, their unaffected siblings, and matched control subjects. RESULTS: On the hardest inhibitory trials in our task, children and adolescents with ADHD had lower accuracy than control subjects, whereas their unaffected siblings did not. Control subjects activated a network of regions, including ventral prefrontal and inferior parietal cortex. Both children and adolescents with ADHD and their unaffected siblings showed decreased activation in these areas, as well as fewer correlations between performance and activation. CONCLUSIONS: These findings suggest that the magnitude of activation during successful inhibitions is sensitive to genetic vulnerability for ADHD in a number of regions, including ventral prefrontal cortex. If this can be replicated in future studies, this suggests that neuroimaging measures related to inhibitory control may be suitable as intermediate phenotypes in studies investigating gene effects in ADHD.

Adolescent↗

Radiological findings in autistic and developmentally delayed children.

PURPOSE: The aim of this study was to evaluate the prevalence of brain abnormalities in a group of young children with developmental disorders, specifically including children that came to the attention of a child psychiatrist before the age of 3 years. METHODS: Forty-five children participated in an MR study (mean age 43 months, SD=12, four females). The study design was approved by the local Medical Ethical Review Board. All parents gave written informed consent. Scans were independently assessed by two board-certified radiologists for malformations of gray and white matter. RESULTS: Cohen's kappa for the consensus between the two raters was 0.79. In 22 children (49%) abnormalities were reported. Four patients (8.5%) had an arachnoid cyst. One female was diagnosed with a Chiari I malformation. Three children show enlarged Virchow-Robin spaces, an increased occurrence when compared to the normal population. CONCLUSIONS: A high rate of intracranial abnormalities was found in this study. Radiological findings do not contribute to the diagnosis of developmental disorders. However, young children with developmental disorders may not be able to express discomfort associated with brain abnormalities, such as a Chiari I malformation. Given the high prevalence of abnormalities in this sample neuroimaging may be a useful tool in clinically assessing children with developmental disorders.

Autistic Disorder↗

No evidence for preferential involvement of medial temporal lobe structures in high-functioning autism.

BACKGROUND: Autism is a neurodevelopmental disorder associated with slight increases in brain volume. There has been some suggestion that medial temporal lobe structures may be preferentially involved in this disorder, although results have not always been consistent. Here, we investigate amygdala and hippocampus volumes in medication-naive subjects with high-functioning autism. METHOD: Whole-brain magnetic resonance imaging scans were acquired from 42 patients and 42 closely matched, healthy control subjects. RESULTS: Amygdala volume did not differ significantly between patients and controls. A significant increase in hippocampal volume was proportional to an increase in overall brain volume. CONCLUSIONS: These results argue against preferential involvement of medial temporal lobe structures in autism, at least in high-functioning medication-naive individuals.

Adolescent↗

A shift from diffuse to focal cortical activity with development.

Recent imaging studies have suggested that developmental changes may parallel aspects of adult learning in cortical activation becoming less diffuse and more focal over time. However, while adult learning studies examine changes within subjects, developmental findings have been based on cross-sectional samples and even comparisons across studies. Here, we used functional MRI in children to test directly for shifts in cortical activity during performance of a cognitive control task, in a combined longitudinal and cross-sectional study. Our longitudinal findings, relative to our cross-sectional ones, show attenuated activation in dorsolateral prefrontal cortical areas, paralleled by increased focal activation in ventral prefrontal regions related to task performance.

Age Factors↗

What have we learned about cognitive development from neuroimaging?

Changes in many domains of cognition occur with development. In this paper, we discuss neuroimaging approaches to understanding these changes at a neural level. We highlight how modern imaging methods such as functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) are being used to examine how cognitive development is supported by the maturation of the brain. Some reports suggest developmental changes in patterns of brain activity appear to involve a shift from diffuse to more focal activation, likely representing a fine-tuning of relevant neural systems with experience. One of the challenges in investigating the interplay between cognitive development and maturation of the brain is to separate the contributions of neural changes specific to development and learning. Examples are given from the developmental neuroimaging literature. The focus is on the development of cognitive control, as the protracted developmental course of this ability into adolescence raises key issues. Finally, the relevance of normative studies for understanding neural and cognitive changes in developmental disorders is discussed.

Adolescent↗

Imaging the developing brain: what have we learned about cognitive development?

The human brain undergoes significant changes in both its structural architecture and functional organization across the life span. Advances in neuroimaging techniques over the past decade have allowed us to track these changes safely in the human in vivo. We review the imaging literature on the neurobiology of cognitive development, focusing specifically on cognitive task-dependent changes observed in brain physiology and anatomy across childhood and adolescence. The findings suggest that cortical function becomes fine-tuned with development. Brain regions associated with more basic functions such as sensory and motor processes mature first, followed by association areas involved in top-down control of behavior.

Adolescent↗

Increased gray-matter volume in medication-naive high-functioning children with autism spectrum disorder.

BACKGROUND: To establish whether high-functioning children with autism spectrum disorder (ASD) have enlarged brains in later childhood, and if so, whether this enlargement is confined to the gray and/or to the white matter and whether it is global or more prominent in specific brain regions. METHOD: Brain MRI scans were acquired from 21 medication-naive, high-functioning children with ASD between 7 and 15 years of age and 21 comparison subjects matched for gender, age, IQ, height, weight, handedness, and parental education, but not pubertal status. RESULTS: Patients showed a significant increase of 6% in intracranium, total brain, cerebral gray matter, cerebellum, and of more than 40% in lateral and third ventricles compared to controls. The cortical gray-matter volume was evenly affected in all lobes. After correction for brain volume, ventricular volumes remained significantly larger in patients. CONCLUSIONS: High-functioning children with ASD showed a global increase in gray-matter, but not white-matter and cerebellar volume, proportional to the increase in brain volume, and a disproportional increase in ventricular volumes, still present after correction for brain volume. Advanced pubertal development in the patients compared to the age-matched controls may have contributed to the findings reported in the present study.

Adolescent↗

Magnetic resonance imaging of boys with attention-deficit/hyperactivity disorder and their unaffected siblings.

OBJECTIVE: To study the influence of increased familial risk for attention-deficit/hyperactivity disorder (ADHD) on brain morphology. METHOD: Volumetric cerebral measures based on whole brain magnetic resonance imaging scans from 30 boys with ADHD, 30 of their unaffected siblings, and 30 matched controls were compared. RESULTS: Both subjects with ADHD and their unaffected siblings displayed reductions in right prefrontal gray matter and left occipital gray and white matter of up to 9.1% (p < 0.05). Right cerebellar volume was reduced by 4.9% in subjects with ADHD (p = 0.026) but not in their unaffected siblings (p = 0.308). A 4.0% reduction in intracranial volume was found in subjects with ADHD (p = 0.031), while a trend was observed in their unaffected siblings (p = 0.068). CONCLUSIONS: The volumetric reductions in cortical gray and white matter in subjects with ADHD are also present in their unaffected siblings, suggesting that they are related to an increased familial risk for the disorder. In contrast, the cerebellum is unaffected in siblings, suggesting that the reduction in volume observed in subjects with ADHD may be more directly related to the pathophysiology of this disorder.

Adolescent↗

Evidence of developmental differences in implicit sequence learning: an fMRI study of children and adults.

Prevailing theories of implicit or unaware learning propose a developmental invariance model, with implicit function maturing early in infancy or childhood despite prolonged improvements in explicit or intentional learning and memory systems across childhood. Neuroimaging studies of adult visuomotor sequence learning have associated fronto-striatal brain regions with implicit learning of spatial sequences. Given evidence of continued development in these brain regions during childhood, we compare implicit sequence learning in adults and 7- to 11-year-old children to examine potential developmental differences in the recruitment of fronto-striatal circuitry during implicit learning. Participants performed a standard serial reaction time task. Stimuli alternately followed a fixed 10-step sequence of locations or were presented in a pseudorandom order of locations. Adults outperformed children, achieving a significantly larger sequence learning effect and showing learning more quickly than children. Age-related differences in activity were observed in the premotor cortex, putamen, hippocampus, inferotemporal cortex, and parietal cortex. We observed differential recruitment of cortical and subcortical motor systems between groups, presumably reflecting age differences in motor response execution. Adults showed greater hippocampal activity for sequence trials, whereas children demonstrated greater signal during random trials. Activity in the right caudate correlated significantly with behavioral measures of implicit learning for both age groups, although adults showed greater signal change than children overall, as would be expected given developmental differences in sequence learning magnitude. These results challenge the idea of developmental invariance in implicit learning and instead support a view of parallel developments in implicit and explicit learning systems.

Adult↗

Differential patterns of striatal activation in young children with and without ADHD.

BACKGROUND: Cognitive control, defined as the ability to suppress inappropriate thoughts and actions, is compromised in attention-deficit/hyperactivity disorder (ADHD). This study examines the neural basis of this deficit. METHODS: We used a paradigm that incorporates a parametric manipulation within a go/nogo task, so that the number of go trials preceding a nogo trial is varied to tax the neural systems underlying cognitive control with increasing levels of interference. RESULTS: Using this paradigm in combination with event-related functional magnetic resonance imaging (fMRI), we show that children without ADHD have increased susceptibility to interference with increasing numbers of go trials preceding a nogo trial, but children with ADHD have difficulty even with a single go trial preceding a nogo trial. In addition, children with ADHD do not activate frontostriatal regions in the same manner as normally developing children, but rather rely on a more diffuse network of regions, including more posterior and dorsolateral prefrontal regions. CONCLUSIONS: Normal immature cognition may be characterized as being susceptible to interference and supported by the maturation of frontostriatal circuitry. ADHD children show a slightly different cognitive profile at 6 to 10 years of age that is paralleled by a relative lack of or delay in the maturation of ventral frontostriatal circuitry.

Attention Deficit Disorder with Hyperactivity↗

A review of the biological bases of ADHD: what have we learned from imaging studies?

Attention Deficit Hyperactivity Disorder (ADHD) is a common and impairing neuropsychiatric disorder with onset at preschool age. Although a significant amount of progress has been made investigating the neurobiology of this disorder, its precise etiology still remains unclear. Converging evidence from studies of the neuropharmacology, genetics, neuropsychology, and neuroimaging of ADHD imply the involvement of fronto-striatal circuitry in ADHD. However, while it does appear that poor inhibitory control and the deficits in fronto-striatal circuitry associated with it are central, there is evidence to suggest that more posterior cerebral areas are also implicated in this disorder. Anatomical studies suggest widespread reductions in volume throughout the cerebrum and cerebellum, while functional imaging studies suggest that affected individuals activate more diffuse areas than controls during the performance of cognitive tasks. The future impact of new MR imaging methodologies on the field is discussed.

Attention Deficit Disorder with Hyperactivity↗