Cerebellar Dysfunction In Attention-Deficit/Hyperactivity Disorder Children: A FMRI Study

ObjectiveThe objective of this study was to explore whether there were differential activations of cerebellum and other brain regions for ADHD children by performing n-back working memory task.Subjects and methods12 ADHD children ( 9 boys, 3 girls; age, mean±standard deviation, 10.5 years + 1.4 years; 7 inattention type, 5 mixed type) and 12 age-, sex-, handedness-, IQ-, and extent of education-matched healthy controls were recruited. None of them had a history of any other neurological psychiatric disorder and any psychotropic medication administration. All subjects participated in a rapid event-related functional magnetic resonance imaging (fMRI) using a Categorial n-Back Working Memory Task.The task was repeated in 3 runs. Each run consisted of 124 stimuli. Stimuli were generated using E-prime software and projected via AVOTEC Projector Manager III onto a rear-projection screen that was secured vertically in the magnet bore. Subjects viewed the images on a titled mirror attached to the head coil. Percent of correct responses and mean reaction time to correct response (mRT) were used as measures of working memory performance.Imaging was performed using a 3.0T scanner (Intera Achieva; Philips Medical Systems, Best, Netherlands). After the acquisition of routine MRI (including T₁-, T₂-and diffusion-weighted imaging) to rule out any incidental pathological abnormalities, whole-brain functional imaging was performed using a gradient-echo echo-planar imaging (EPI) pulse sequence (32 axial slices parallel to the anterior commissure-posterior commissure (AC-PC) line, TR/TE = 2000ms/30ms, 4mm slice thickness without a gap, FOV=230mm, 64×64 matrix). High-resolution 3D structural images were acquired (GRE, TR/TE = 9.6ms/4.6ms, 128 slices with 1.2mm slice thickness, FOV=230mm, 256×256 matrix).Behavioral analyses were analyzed using SPSS 10.0 software with two-tailed t tests at a significance level of P=0.05. fMRI data were preprocessed and analyzed using SPM2. The activated brain regions were read out by using Talairach software (version 1.1). The correlation between activation of each group and the percent of correct responses, mean reaction time to correct response were also analyzed at a significance level of P=0.05.ResultsSignificant difference of mRT and the percent of correct responses were observed between two groups. ADHD children had more errors (the percent of correct response: ADHD,[78.9±5.5]%; controls,[83.4±4.9]%) and longer mRT (ADHD,[695.3±76.3] ms; control, [645.9±89.0]ms) than healthy controls (P<0.01, P<0.05 respectively).Within-group analysis, control group showed significant activation in bilateral cerebellum-posterior lobe, right middle frontal gyrus (BA6,8,46), left inferior parietal lobe (BA40), right superior/inferior parietal lobe (BA40/7), left cuneus (BA19) and right cuneus/inferior occipital gyrus (BA18/19), consistent with patterns of activation described in previous literatures. And in ADHD group, only right cerebellum-posterior lobe and right parietal lobe-postcentral gyrus (BA40) were activated.Between-group analysis, difference between two groups were significant only in the left posterior cerebellar lobe (at the P<0.01, extent, 5 voxels threshold). It was our noticeable finding that activation was weaker for ADHD children than controls in the left, not right or bilateral, posterior cerebellar lobe. There were no regions where activation was greater for ADHD children than controls. Correlation analyses, no significant correlations (P>0.05) were found between the activation of cerebellum and mRT, the percent of correct response for each group.ConclusionsThis study suggest that there was dysfunction in left cerebellar lobe for children with ADHD. The left-lateralized dysfunction of the cerebellum and the functional disconnection in the frontal-thalamic-cerebellar circuit might be associated with cognitive abnormality in patients with ADHD.