Objective To perform a comprehensive meta-analysis of task-based functional MRI studies of Attention-Deficit/Hyperactivity Disorder (ADHD). Method PubMed, Ovid, EMBASE, Web of Science, ERIC, CINHAL, and NeuroSynth were searched for studies published through 06/30/2011. Significant differences in activation of brain regions between individuals with ADHD and comparisons were detected using activation likelihood estimation meta-analysis (p<0.05, corrected). Dysfunctional regions in ADHD were related to seven reference neuronal systems. We performed a set of meta-analyses focused on age groups (children; adults), clinical characteristics (history of stimulant treatment; presence of psychiatric comorbidities), and specific neuropsychological tasks (inhibition; working memory; vigilance/attention). Results Fifty-five studies were included (39 in children, 16 in adults). In children, hypoactivation in ADHD vs. comparisons was found mostly in systems involved in executive functions (frontoparietal network) and attention (ventral attentional network). Significant hyperactivation in ADHD vs. comparisons was observed predominantly within the default, ventral attention, and somatomotor networks. In adults, ADHD-related hypoactivation was predominant in the frontoparietal system, while ADHD-related hyperactivation was present in the visual, dorsal attention, and default networks. Significant ADHD-related dysfunction largely reflected task features and was detected even in the absence of comorbid mental disorders or history of stimulant treatment. Conclusions A growing literature provides evidence of ADHD-related dysfunction within multiple neuronal systems involved in higher-level cognitive functions but also in sensorimotor processes, including the visual system, and in the default network. This meta-analytic evidence extends early models of ADHD pathophysiology focused on prefrontal-striatal circuits.

14Centre référent pour le diagnostic des troubles du langage et des apprentissages, Département de pédiatrie, CHU Nord, Grenoble, France; Background: The relationship between phoneme awareness, rapid automatized naming (RAN), verbal short-term/working memory (ST/WM) and diagnostic category is investigated in control and dyslexic children, and the extent to which this depends on orthographic complexity. Methods: General cognitive, phonological and literacy skills were tested in 1,138 control and 1,114 dyslexic children speaking six different languages spanning a large range of orthographic complexity (Finnish, Hungarian, German, Dutch, French, English). Results: Phoneme deletion and RAN were strong concurrent predictors of developmental dyslexia, while verbal ST/WM and general verbal abilities played a comparatively minor role. In logistic regression models, more participants were classified correctly when orthography was more complex. The impact of phoneme deletion and RAN-digits was stronger in complex than in less complex orthographies. Conclusions: Findings are largely consistent with the literature on predictors of dyslexia and literacy skills, while uniquely demonstrating how orthographic complexity exacerbates some symptoms of dyslexia.

Background Emerging neuroscientific and genetic findings emphasize the dimensional rather than the categorical aspects of psychiatric disorders. However, the integration of dimensional approaches within the current categorical diagnostic framework remains unclear. Here, we used resting state fMRI (R-fMRI) to examine whether dimensional measures of psychiatric symptomatology capture brain-behavior relationships unaccounted for by categorical diagnoses. Additionally, we examined whether dimensional brain-behavior relationships are modified by the presence of a categorically defined illness, Attention-Deficit/Hyperactivity Disorder (ADHD). Methods R-fMRI scans were collected from 37 typically developing children (aged 10.2±2; 21 females) and 37 children meeting DSM-IV-TR criteria for ADHD (9.7±2; 11 females). Parent-rated Child Behavior Checklist Externalizing and Internalizing scores served as dimensional measures in our analyses of default network (DN) resting state functional connectivity (RSFC). Results Regardless of diagnosis, we observed several significant relationships between DN RSFC and both Internalizing and Externalizing scores. Increased Internalizing scores were associated with stronger positive intra-DN RSFC, while increased Externalizing scores were associated with reduced negative RSFC between DN and “task-positive” regions such as dorsal anterior cingulate cortex. Several of these brain-behavior relationships differed depending on the categorical presence of ADHD. Conclusions Our findings suggest that while categorical diagnostic boundaries provide an inadequate basis for understanding the pathophysiology of psychiatric disorders, psychiatric illness cannot be viewed simply as an extreme of typical neural or behavioral function. Efforts to understand the neural underpinnings of psychiatric illness should incorporate both categorical and dimensional clinical assessments.

In the Neurofibromatosis type 1 (NF1) mouse model, lovastatin, used clinically for hypercholesterolemia, improves cognitive dysfunction. While such impairment has been studied in NF1, the neural substrates remain unclear. The aim of this imaging add-on to a phase-1 open-label trial was to examine the effect of lovastatin on Default Network (DN) resting state functional connectivity (RSFC). Seven children with NF1 (aged 11.9±2.2; 1 female) were treated with lovastatin once daily for 12 weeks. A 7-minute 3-Tesla echo-planar-imaging scan was collected one day before beginning treatment (off-drug) and the last day of treatment (on-drug) while performing a Flanker task. After regressing-out task-associated variance, we used the residual time series as “continuous resting-state data” for RSFC analyses using 11 DN regions of interest. For qualitative comparisons, we included a group of 19 typically developing children (TDC) collected elsewhere. In the on-drug condition, lovastatin increased long-range positive RSFC within DN core regions (i.e., anterior medial prefrontal cortex and posterior cingulate cortex, PCC). In addition, lovastatin produced less diffuse local RSFC in the dorsomedial prefrontal cortex and PCC. The pattern of RSFC observed in the NF1 participants when on-drug closely resembled the RSFC patterns exhibited by the TDC. Lovastatin administration in this open trial regulated anterior-posterior long-range and local RSFC within the DN. These preliminary results are consistent with a role for lovastatin in normalization of developmental processes and with apparent benefits in a mouse NF1 model.

Learning disabilities represent the main childhood complication in neurofibromatosis type 1 (NF1). Patients frequently exhibit T2-weighted hyperintensities called unidentified bright objects (UBOs) on brain magnetic resonance imaging (MRI), with unclear relationship to such cognitive disabilities. This study aimed to determine whether thalamo-striatal UBOs correlate with cognitive disturbances. Thirty-seven NF1 children were studied: 24 with UBOs (18 of which were thalamo-striatal UBOs), and 13 without UBOs. NF1 subjects carrying thalamo-striatal UBOs had significantly lower IQs and visuospatial performances than those without UBOs in this location. These results suggest that UBOs may contribute to NF1 cognitive impairments through thalamo-cortical dysfunction.