Audiovisual Multisensory Integration and Evoked Potentials in Young Adults With and Without Attention-Deficit/Hyperactivity Disorder

Various anatomic brain abnormalities have been reported for attention-deficit/hyperactivity disorder (ADHD), with varying methods, small samples, cross-sectional designs, and without accounting for stimulant drug exposure. To compare regional brain volumes at initial scan and their change over time in medicated and previously unmedicated male and female patients with ADHD and healthy controls. Case-control study conducted from 1991-2001 at the National Institute of Mental Health, Bethesda, Md, of 152 children and adolescents with ADHD (age range, 5-18 years) and 139 age- and sex-matched controls (age range, 4.5-19 years) recruited from the local community, who contributed 544 anatomic magnetic resonance images. Using completely automated methods, initial volumes and prospective age-related changes of total cerebrum, cerebellum, gray and white matter for the 4 major lobes, and caudate nucleus of the brain were compared in patients and controls. On initial scan, patients with ADHD had significantly smaller brain volumes in all regions, even after adjustment for significant covariates. This global difference was reflected in smaller total cerebral volumes (-3.2%, adjusted F(1,280) = 8.30, P =.004) and in significantly smaller cerebellar volumes (-3.5%, adjusted F(1,280) = 12.29, P =.001). Compared with controls, previously unmedicated children with ADHD demonstrated significantly smaller total cerebral volumes (overall F(2,288) = 6.65; all pairwise comparisons Bonferroni corrected, -5.8%; P =.002) and cerebellar volumes (-6.2%, F( 2,288) = 8.97, P<.001). Unmedicated children with ADHD also exhibited strikingly smaller total white matter volumes (F(2,288) = 11.65) compared with controls (-10.7%, P<.001) and with medicated children with ADHD (-8.9%, P<.001). Volumetric abnormalities persisted with age in total and regional cerebral measures (P =.002) and in the cerebellum (P =.003). Caudate nucleus volumes were initially abnormal for patients with ADHD (P =.05), but diagnostic differences disappeared as caudate volumes decreased for patients and controls during adolescence. Results were comparable for male and female patients on all measures. Frontal and temporal gray matter, caudate, and cerebellar volumes correlated significantly with parent- and clinician-rated severity measures within the ADHD sample (Pearson coefficients between -0.16 and -0.26; all P values were <.05). Developmental trajectories for all structures, except caudate, remain roughly parallel for patients and controls during childhood and adolescence, suggesting that genetic and/or early environmental influences on brain development in ADHD are fixed, nonprogressive, and unrelated to stimulant treatment.

The aim of this study was (1) to provide behavioral evidence for multimodal feature integration in an object recognition task in humans and (2) to characterize the processing stages and the neural structures where multisensory interactions take place. Event-related potentials (ERPs) were recorded from 30 scalp electrodes while subjects performed a forced-choice reaction-time categorization task: At each trial, the subjects had to indicate which of two objects was presented by pressing one of two keys. The two objects were defined by auditory features alone, visual features alone, or the combination of auditory and visual features. Subjects were more accurate and rapid at identifying multimodal than unimodal objects. Spatiotemporal analysis of ERPs and scalp current densities revealed several auditory-visual interaction components temporally, spatially, and functionally distinct before 200 msec poststimulus. The effects observed were (1) in visual areas, new neural activities (as early as 40 msec poststimulus) and modulation (amplitude decrease) of the N185 wave to unimodal visual stimulus, (2) in the auditory cortex, modulation (amplitude increase) of subcomponents of the unimodal auditory N1 wave around 90 to 110 msec, and (3) new neural activity over the right fronto-temporal area (140 to 165 msec). Furthermore, when the subjects were separated into two groups according to their dominant modality to perform the task in unimodal conditions (shortest reaction time criteria), the integration effects were found to be similar for the two groups over the nonspecific fronto-temporal areas, but they clearly differed in the sensory-specific cortices, affecting predominantly the sensory areas of the nondominant modality. Taken together, the results indicate that multisensory integration is mediated by flexible, highly adaptive physiological processes that can take place very early in the sensory processing chain and operate in both sensory-specific and nonspecific cortical structures in different ways.

Although there are many structural neuroimaging studies of attention-deficit/hyperactivity disorder (ADHD) in children, there are inconsistencies across studies and no consensus regarding which brain regions show the most robust area or volumetric reductions relative to control subjects. Our goal was to statistically analyze structural imaging data via a meta-analysis to help resolve these issues. We searched the MEDLINE and PsycINFO databases through January 2005. Studies must have been written in English, used magnetic resonance imaging, and presented the means and standard deviations of regions assessed. Data were extracted by one of the authors and verified independently by another author. Analyses were performed using STATA with metan, metabias, and metainf programs. A meta-analysis including all regions across all studies indicated global reductions for ADHD subjects compared with control subjects, standardized mean difference=.408, p<.001. Regions most frequently assessed and showing the largest differences included cerebellar regions, the splenium of the corpus callosum, total and right cerebral volume, and right caudate. Several frontal regions assessed in only two studies also showed large significant differences. This meta-analysis provides a quantitative analysis of neuroanatomical abnormalities in ADHD and information that can be used to guide future studies.