Event-related fMRI was employed to characterize differences in brain activation between children ages 8-12 and adults related to two forms of cognitive control: interference suppression and response inhibition. Children were more susceptible to interference and less able to inhibit inappropriate responses than were adults. Effective interference suppression in children was associated with prefrontal activation in the opposite hemisphere relative to adults. In contrast, effective response inhibition in children was associated with activation of posterior, but not prefrontal, regions activated by adults. Children failed to activate a region in right ventrolateral prefrontal cortex that was recruited for both types of cognitive control by adults. Thus, children exhibited immature prefrontal activation that varied according to the type of cognitive control required.

Functional MRI revealed differences between children with Attention Deficit Hyperactivity Disorder (ADHD) and healthy controls in their frontal-striatal function and its modulation by methylphenidate during response inhibition. Children performed two go͞no-go tasks with and without drug. ADHD children had impaired inhibitory control on both tasks. Off-drug frontal-striatal activation during response inhibition differed between ADHD and healthy children: ADHD children had greater frontal activation on one task and reduced striatal activation on the other task. Drug effects differed between ADHD and healthy children: The drug improved response inhibition in both groups on one task and only in ADHD children on the other task. The drug modulated brain activation during response inhibition on only one task: It increased frontal activation to an equal extent in both groups. In contrast, it increased striatal activation in ADHD children but reduced it in healthy children. These results suggest that ADHD is characterized by atypical frontalstriatal function and that methylphenidate affects striatal activation differently in ADHD than in healthy children.

Prefrontal cortical function was examined during semantic encoding and repetition priming using functional magnetic resonance imaging (fMRI), a noninvasive technique for localizing regional changes in blood oxygenation, a correlate of neural activity. Words studied in a semantic (deep) encoding condition were better remembered than words studied in both easier and more difficult nonsemantic (shallow) encoding conditions, with difficulty indexed by response time. The left inferior prefrontal cortex (LIPC) (Brodmann's areas 45, 46, 47) showed increased activation during semantic encoding relative to nonsemantic encoding regardless of the relative difficulty of the nonsemantic encoding task. Therefore, LIPC activation appears to be related to semantic encoding and not task difficulty. Semantic encoding decisions are performed faster the second time words are presented. This represents semantic repetition priming, a facilitation in semantic processing for previously encoded words that is not dependent on intentional recollection. The same LIPC area activated during semantic encoding showed decreased activation during repeated semantic encoding relative to initial semantic encoding of the same words. This decrease in activation during repeated encoding was process specific; it occurred when words were semantically reprocessed but not when words were nonsemantically reprocessed. The results were apparent in both individual and averaged functional maps. These findings suggest that the LIPC is part of a semantic executive system that contributes to the on-line retrieval of semantic information.

Diffusion tensor imaging (DTI) measures diffusion of molecular water, which can be used to calculate indices of white matter integrity. Early DTI studies of aging primarily focused on two global measures of integrity; the average rate (mean diffusivity, MD) and orientation coherence (fractional anisotropy, FA) of diffusion. More recent studies have added measures of water movement parallel (axial diffusivity, AD) and perpendicular (radial diffusivity, RD) to the primary diffusion direction, which are thought to reflect the neural bases of age differences in diffusion (i.e., axonal shrinkage and demyelination, respectively). In the present study, patterns of age differences in white matter integrity were assessed by comparing younger and healthy older adults on multiple measures of integrity (FA, AD, RD). Results revealed two commonly reported patterns (Radial Increase Only and Radial/Axial Increase), and one relatively novel pattern (Radial Increase/Axial Decrease) that varied by brain region and may reflect differential aging of microstructural (e.g., degree of myelination) and macrostructural (e.g., coherence of fiber orientation) properties of white matter. In addition, larger age differences in FA in frontal white matter were consistent with the anterior-posterior gradient of age differences in white matter integrity. Together, these findings complement other recent studies in providing information about patterns of diffusivity that are characteristic of healthy aging. KeywordsAging; axial diffusivity; DTI; fractional anisotropy; radial diffusivity Brain aging research has been dominated by examinations of age-related differences in the structure and function of gray matter (Cabeza, et al. 2005), with the other half of the brainwhite matter-having been largely ignored. The lack of attention to white matter aging in the past likely resulted from limitations in imaging technology, because the relatively recent Address correspondence to: Ilana J. Bennett, Georgetown University, Department of Psychology, 301 N White Gravenor Building, Washington, DC 20057, PH: 202-687-4099, FX: 202-687-6050, ijb5@georgetown.edu. Preliminary findings from this project were presented at the Society for Neuroscience Conferences in San Diego, CA in November, 2007 and Washington, DC in November, 2008; NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript advent of diffusion tensor imaging (DTI) has led to widespread in interest in age-related changes in white matter.DTI is a magnetic resonance imaging (MRI) technique that measures the diffusion of molecular water (Basser, et al. 1994;. Water diffuses 3-7 times more rapidly along the length of axons aligned in white matter tracts compared to movement perpendicular to the axons (Le Bihan 2003; because the latter is restricted by axonal cell membranes, myelin sheaths, and neurofilaments (Beaulieu 2002). Various properties of water diffusion can be calculated from DTI-based eigenvalue measures (λ1, λ2, and λ3; which indicate the rate of diffusion along the...

Summary Autism spectrum disorder (ASD), a neurodevelopmental disorder affecting nearly 1 in 88 children, is thought to result from aberrant brain connectivity. Remarkably, there have been no systematic attempts to characterize whole-brain connectivity in children with ASD. Here, we use neuroimaging to show there are more instances of greater functional connectivity in the brains of children with ASD compared with typically developing children. Hyper-connectivity in ASD was observed at the whole-brain and subsystems level, across long- and short-range connections, and was associated with higher levels of fluctuations in regional brain signals. Brain hyper-connectivity predicted symptom severity in ASD such that children with greater functional connectivity exhibited more severe social deficits. We replicated these findings in two additional independent cohorts, demonstrating again that at earlier ages, the brain in ASD is largely functionally hyper-connected in ways that contribute to social dysfunction. Our findings provide novel insights into brain mechanisms underlying childhood autism.