Howard Florey Institute and Centre for Neuroscience and Academic Child Psychiatry Unit, Department of Paediatrics, University of Melbourne, and Department of Psychology, Monash University, Victoria, Australia
Academic Child Psychiatry Unit, Department of Paediatrics, University of Melbourne and Royal Childrens Hospital and Murdoch Childrens Research Institute, Parkville, Victoria, Australia
Department of Psychological Medicine, Monash University, Victoria, Australia
Howard Florey Institute and Centre for Neuroscience, University of Melbourne
Department of Human Development and Family Studies, Texas Tech University, Lubbock, Texas, USA
Department of Psychology, Monash University, Victoria, Australia
Howard Florey Institute and Centre for Neuroscience, University of Melbourne and Brain Research Institute, Austin Health Heidelberg West, 3081, Victoria, Australia
Correspondence: Professor A. Vance, Academic Child Psychiatry Unit, Department of Paediatrics, University of Melbourne, Parkville, 3052, Victoria, Australia. E-mail: avance{at}unimelb.edu.au
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ABSTRACT |
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INTRODUCTION |
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To date, the specific patterns of activation of fronto-parietal brain areas in adolescents with ADHD-CT compared with matched healthy controls have not been reported. Mental rotation tasks are known to activate the superior parietal areas (Parsons, 2003) and the middle frontal areas (Booth et al, 2000), in healthy children and adults. In this study we used a functional magnetic resonance imaging (fMRI) mental rotation task paradigm to examine the patterns of activation of these brain areas in adolescents with ADHD-CT.
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METHOD |
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Participants were presented 18 baseline and 18 mental rotation trials, each comprising one target stimulus together with four test stimuli, with speed and accuracy instructions. Participants were required to indicate by button-press which test stimulus matched the target. The stimuli consisted of Shepard-Metzler-type three-dimensional cube objects, with target and matching stimuli differing by between 45° and 180° rotation. The baseline condition required judgement of which spatial Fourier transformed noise patch of four was a best visual match to the target. For each trial, stimuli were presented for 10 s with a 1 s inter-stimulus interval. Groups of three baseline trials alternating with three rotation trials were presented in 12 blocks over a total scan duration of 6 min 36 s.
Data were acquired on a 3.0 Tesla GE Signa Horizon LX magnetic resonance imaging (MRI) scanner (GE Medical Systems, Milwaukee, Wisconsin, USA). Gradient echo planar images were acquired (repetition time 3000 ms, echo time 40 ms, 128 x 128 matrix at 1.875 x 1.875 mm2, 22 slices at 4.5+0.5 mm thickness); 136 volumes were acquired per scanning session. High-resolution structural MRI images were also acquired for each participant (repetition time 120 ms, 256 x 256 x 128 matrix, voxel=0.9 x 0.9 mm2, slice thickness=1.4 mm). Functional images were realigned, spatially normalised to Talairach space, and spatially smoothed (full width at half maximum=8 mm) using general linear model analysis using SPM2 software for Linux (University College London, UK). For SPM2 analysis, each stimulus was modelled as a discrete event, using the SPM2 canonical haemodynamic response function with temporal and dispersion derivatives. Realignment parameters were also included as regressors in the model to account for residual signal variance related to the individuals head motion. Group analysis was based on random-effects models, using single-sample t-tests to examine activation in ADHD-CT and control groups separately, and independent t-tests to examine differences between groups.
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RESULTS |
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During mental rotation compared with the baseline task (see figure published as a data supplement to the online version of this paper), the ADHD-CT group showed significant activation (cluster level Pcorr<0.05, voxel level Puncorr<0.001) in the right premotor cortex (BA 6; coordinates 27, 9, 54), as well as pre- and post-central gyri (BA 6/3), and the right frontal cortex including the insula (BA 13; 36, 9, 18) and dorsal regions of inferior and middle frontal gyri (9/46; 45, 18, 21). Activation was also found occipitally in the left cuneus (BA 19; 15, 90, 24) and in the cerebellum. The control group similarly showed significant activation in the right premotor cortex (BA 6; 21, 6, 51) as well as the occipital cortex (right precuneus BA 7; 15, 75, 42 and BA 18; 30, 84, 3) and the right inferior parietal cortex (BA 40; 48, 39, 3). Significant activation for controls was also found in the anterior cingulate (BA 32/8; 3, 27, 39), which was not apparent for the ADHD-CT group, as well as bilateral activation in dorsal regions of the inferior/middle frontal gyri (51, 3, 24 and 39, 12, 80) and in a ventral region of the right inferior frontal gyrus (BA 11; 24, 27, 18).
Random effects group analysis showed significantly greater activation (cluster level Puncorr<0.05, voxel level Puncorr<0.01) for the control compared with ADHD-CT participants in the left caudate head and left prefrontal cortex, including superior and inferior frontal gyri (BA 10/46), as well as the right inferior frontal gyrus (BA 47), also extending into the right caudate head, the bilateral visual association cortex (BA 19), extending rostrally to the right superior temporal gyrus (BA 39) and in the right superior and inferior parietal lobules (BA 7/40). In contrast, the ADHD-CT group showed significantly more activation in the left middle and superior temporal gyri (BA 13/39/41), medial areas including the posterior cingulate (BA 31) and the medial superior prefrontal cortex (BA 8/10).
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DISCUSSION |
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In conclusion, these findings suggest a widespread maturational lag affecting fronto-parietal functional neural systems associated with more diffuse, inefficient activation of the midline attentional cortical networks. This is consistent with emerging theoretical models of immature, inefficient neural networks being replaced by mature, efficient neural networks that then attempt to maintain themselves across the entire lifespan (Rakic, 2004).
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ACKNOWLEDGMENTS |
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REFERENCES |
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Received for publication September 13, 2004. Revision received December 13, 2004. Accepted for publication December 21, 2004.
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