The quantitative overflow measures used in this study support past qualitative findings that motor overflow persists to a greater degree in children with ADHD than in age-matched TD peers. The quantitative findings further suggest that persistence of mirror overflow is more prominent during task execution of the nondominant hand and reveal gender-based differences in developmental neural systems critical to motor control. These quantitative measures will assist future physiologic investigation of the brain basis of motor control in ADHD.

The ability to examine associations between neuropsychiatric conditions and functionally relevant frontal lobe sub-regions is a fundamental goal in neuropsychiatry, but methods for identifying frontal sub-regions in MR (magnetic resonance) images are not well established. Prior published techniques have principally defined gyral regions that do not necessarily correspond to known functional divisions. We present a method in which sulcal-gyral landmarks are used to manually delimit functionally relevant regions within the frontal lobe: primary motor cortex, anterior cingulate, deep white matter, premotor cortex regions (supplementary motor complex (SMC), frontal eye field and lateral premotor cortex) and prefrontal cortex (PFC) regions (medial PFC, dorsolateral PFC (DLPFC), inferior PFC, lateral orbitofrontal cortex (OFC) and medial OFC). Feasibility was tested by applying the protocol to brain MR data from 15 boys with ADHD and 15 typically developing controls, 8-12 years old. Intra-and inter-rater intraclass correlation coefficients were calculated using parcellation volumes from a subset of that group. Inter-rater results for the 22 hemisphere specific sub-regions ranged from 0.724 to 0.997, with all but six values above 0.9. Boys with ADHD showed significantly smaller left hemisphere SMC and DLPFC volumes after normalization for total cerebral volume. These findings support the method as a reliable and valid technique for parcellating the frontal lobe into functionally relevant subregions. KeywordsADHD; Children; Cortex; Prefrontal; Premotor; Segmentation; Supplementary Motor Complex Corresponding Author: Walter E. Kaufmann, Kennedy Krieger Institute, 3901 Greenspring Ave., Baltimore, MD 21211, Phone: 443-923-2789, Fax: 443-923-7696, Email: kaufmann@kennedykrieger.org. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access 1.) INTRODUCTIONThe frontal lobe is the region of the brain associated with executive control and planning, including functions such as response inhibition and working memory (Tekin & Cummings, 2002;Alvarez & Emory, 2006). The frontal lobe is also involved in motivational aspects of behavior and high-order motor control (Tekin et al., 2002;Ashe et al., 2006;Graziano & Aflalo, 2007). Due to this wide range of complex brain functions, abnormalities in frontal lobe structure and function have been hypothesized to contribute to many neuropsychiatric disorders, including obsessive-compulsive disorder (OCD), schizophrenia, depression and bipolar disorder (Tekin et al., 2002;Yamasue et al., 2004;Suzuki et al., 2005;Shad et al., 2006). F...

The current study examined regional frontal lobe volumes based on functionally relevant subdivisions in contemporaneously recruited samples of boys and girls with and without attention-deficit/hyperactivity disorder (ADHD). Forty-four boys (21 ADHD, 23 control) and 42 girls (21 ADHD, 21 control), ages 8–13 years, participated. Sulcal–gyral landmarks were used to manually delimit functionally relevant regions within the frontal lobe: primary motor cortex, anterior cingulate, deep white matter, premotor regions [supplementary motor complex (SMC), frontal eye field, lateral premotor cortex (LPM)], and prefrontal cortex (PFC) regions [medial PFC, dorsolateral PFC (DLPFC), inferior PFC, lateral orbitofrontal cortex (OFC), and medial OFC]. Compared to sex-matched controls, boys and girls with ADHD showed reduced volumes (gray and white matter) in the left SMC. Conversely, girls (but not boys) with ADHD showed reduced gray matter volume in left LPM; while boys (but not girls) with ADHD showed reduced white matter volume in left medial PFC. Reduced left SMC gray matter volumes predicted increased go/no–go commission rate in children with ADHD. Reduced left LPM gray matter volumes predicted increased go/no–go variability, but only among girls with ADHD. Results highlight different patterns of anomalous frontal lobe development among boys and girls with ADHD beyond that detected by measuring whole lobar volumes.

Magnetic resonance imaging (MRI) has been used to analyze highly specific volumetric and morphological features of the brains of individuals with autism spectrum disorder (ASD). To date, there are few comprehensive studies examining the prevalence of neuroradiologic findings seen on routine MRI scans in children with ASD. This study examined the prevalence of neuroradiologic findings in children with high functioning ASD, and compared these rates to those in children with Attention-Deficit/Hyperactivity Disorder (ADHD) and children who are typically developing (TD). Results showed that approximately 90% of children had normal MRI scans. There was no significant effect of diagnosis on the total number of neuroradiological findings or the number of specific brain findings. Implications and future research directions are discussed.

Attention-deficit/Hyperactivity Disorder (ADHD) is a developmental disorder which, by current definition, has onset prior to age 7 years. MRI studies have provided some insight into brain differences associated with ADHD, but thus far have almost exclusively focused on children ages 7 years and older. To better understand the neurobiological development of ADHD, cortical and subcortical brain development should be systematically examined in younger children presenting with symptoms of the disorder. High resolution anatomical (MPRAGE) images, acquired on a 3.0T scanner, were analyzed in a total of 26 preschoolers, ages 4–5 years (13 with ADHD, 13 controls, matched on age and sex). The ADHD sample was diagnosed using DSM-IV criteria, and screened for language disorders. Cortical regions were delineated and measured using automated methods in Freesurfer; basal ganglia structures were manually delineated. Children with ADHD showed significantly reduced caudate volumes bilaterally; in contrast, there were no significant group differences in cortical volume or thickness in this age range. After controlling for age and total cerebral volume, left caudate volume was a significant predictor of hyperactive/impulsive, but not inattentive symptom severity. Anomalous basal ganglia, particularly caudate, development appears to play an important role among children presenting with early onset symptoms of ADHD.

Examination of associations between specific disorders and physical properties of functionally relevant frontal lobe sub-regions is a fundamental goal in neuropsychiatry. Here we present and evaluate automated methods of frontal lobe parcellation with the programs FreeSurfer(FS) and TOADS-CRUISE(T-C), based on the manual method described in Ranta et al. (2009) in which sulcal-gyral landmarks were used to manually delimit functionally relevant regions within the frontal lobe: i.e., primary motor cortex, anterior cingulate, deep white matter, premotor cortex regions (supplementary motor complex, frontal eye field and lateral premotor cortex) and prefrontal cortex (PFC) regions (medial PFC, dorsolateral PFC, inferior PFC, lateral orbitofrontal cortex (OFC) and medial OFC). Dice's coefficient, a measure of overlap, and percent volume difference were used to measure the reliability between manual and automated delineations for each frontal lobe region. For FS, mean Dice's coefficient for all regions was 0.75 and percent volume difference was 21.2%. For T-C the mean Dice's coefficient was 0.77 and the mean percent volume difference for all regions was 20.2%. These results, along with a high degree of agreement between the two automated methods (mean Dice's coefficient = 0.81, percent volume difference = 12.4%) and a proof-of-principle group difference analysis that highlights the consistency and sensitivity of the automated methods, indicate that the automated methods are valid techniques for parcellation of the frontal lobe into functionally relevant sub-regions. Thus, the methodology has the potential to increase efficiency, statistical power and reproducibility for population analyses of neuropsychiatric disorders with hypothesized frontal lobe contributions.