Attention deficit hyperactivity disorder (ADHD) comprises a deficit in behavioral inhibition. A theoretical model is constructed that links inhibition to 4 executive neuropsychological functions that appear to depend on it for their effective execution: (a) working memory, (b) self-regulation of affect-motivation-arousal, (c) internalization of speech, and (d) reconstitution (behavioral analysis and synthesis). Extended to ADHD, the model predicts that ADHD should be associated with secondary impairments in these 4 executive abilities and the motor control they afford. The author reviews evidence for each of these domains of functioning and finds it to be strongest for deficits in behavioral inhibition, working memory, regulation of motivation, and motor control in those with ADHD. Although the model is promising as a potential theory of self-control and ADHD, far more research is required to evaluate its merits and the many predictions it makes about ADHD.

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Behavioral inhibition, sustained attention, and executive functions: Constructing a unifying theory of ADHD.

Pediatric neuroimaging studies1,2,3,4,5, up to now exclusively cross sectional, identify linear decreases in cortical gray matter and increases in white matter across ages 4 to 20. In this large-scale longitudinal pediatric neuroimaging study, we confirmed linear increases in white matter, but demonstrated nonlinear changes in cortical gray matter, with a preadolescent increase followed by a postadolescent decrease. These changes in cortical gray matter were regionally specific, with developmental curves for the frontal and parietal lobe peaking at about age 12 and for the temporal lobe at about age 16, whereas cortical gray matter continued to increase in the occipital lobe through age 20.

Brain development during childhood and adolescence: a longitudinal MRI study.

The adolescent brain and age-related behavioral manifestations

We report the dynamic anatomical sequence of human cortical gray matter development between the age of 4–21 years using quantitative four-dimensional maps and time-lapse sequences. Thirteen healthy children for whom anatomic brain MRI scans were obtained every 2 years, for 8–10 years, were studied. By using models of the cortical surface and sulcal landmarks and a statistical model for gray matter density, human cortical development could be visualized across the age range in a spatiotemporally detailed time-lapse sequence. The resulting time-lapse “movies” reveal that (i) higher-order association cortices mature only after lower-order somatosensory and visual cortices, the functions of which they integrate, are developed, and (ii) phylogenetically older brain areas mature earlier than newer ones. Direct comparison with normal cortical development may help understanding of some neurodevelopmental disorders such as childhood-onset schizophrenia or autism.

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Dynamic mapping of human cortical development during childhood through early adulthood

Chronic exposure to stress hormones, whether it occurs during the prenatal period, infancy, childhood, adolescence, adulthood or aging, has an impact on brain structures involved in cognition and mental health. However, the specific effects on the brain, behaviour and cognition emerge as a function of the timing and the duration of the exposure, and some also depend on the interaction between gene effects and previous exposure to environmental adversity. Advances in animal and human studies have made it possible to synthesize these findings, and in this Review a model is developed to explain why different disorders emerge in individuals exposed to stress at different times in their lives.

Effects of stress throughout the lifespan on the brain, behaviour and cognition

Background: Anatomic magnetic resonance imaging (MRI) studies of attention-deficit hyperactivity disorder (ADHD) have been limited by small samples or measurement of single brain regions. Since the neuropsychological deficits in ADHD implicate a network linking basal ganglia and frontal regions, 12 subcortical and cortical regions and their symmetries were measured to determine if these structures best distinguished ADHD. Method: Anatomic brain MRIs for 57 boys with ADHD and 55 healthy matched controls, aged 5 to 18 years, were obtained using a 1.5-T scanner with contiguous 2-mm sections. Volumetric measures of the cerebrum, caudate nucleus, putamen, globus pallidus, amygdala, hippocampus, temporal lobe, cerebellum; a measure of prefrontal cortex; and related right-left asymmetries were examined along with midsagittal area measures of the cerebellum and corpus callosum. Interrater reliabilities were.82 or greater for all MRI measures. Results: Subjects with ADHD had a 4.7% smaller total cerebral volume ( P =.02). Analysis of covariance for total cerebral volume demonstrated a significant loss of normal right>left asymmetry in the caudate ( P =.006), smaller right globus pallidus ( P =.005), smaller right anterior frontal region ( P =.02), smaller cerebellum ( P =.05), and reversal of normal lateral ventricular asymmetry ( P =.03) in the ADHD group. The normal age-related decrease in caudate volume was not seen, and increases in lateral ventricular volumes were significantly diminished in ADHD. Conclusion: This first comprehensive morphometric analysis is consistent with hypothesized dysfunction of right-sided prefrontal-striatal systems in ADHD.

Quantitative Brain Magnetic Resonance Imaging in Attention-Deficit Hyperactivity Disorder

Clinical, neuroanatomic, neurobehavioral, and functional brain-imaging studies suggest a role for the cerebellum in cognitive functions, including attention. However, the cerebellum has not been systematically studied in attention-deficit hyperactivity disorder (ADHD). We quantified the cerebellar and vermal volumes, and the midsagittal areas of three vermal regions, from MRIs of 46 right-handed boys with ADHD and 47 matched healthy controls. Vermal volume was significantly less in the boys with ADHD. This reduction involved mainly the posterior inferior lobe (lobules VIII to X) but not the posterior superior lobe (lobules VI to VII). These results remained significant even after adjustment for brain volume and IQ. A cerebello-thalamo-prefrontal circuit dysfunction may subserve the motor control, inhibition, and executive function deficits encountered in ADHD.

Cerebellum in attention-deficit hyperactivity disorder: a morphometric MRI study.

Objective: Because the caudate nuclei receive inputs from cortical regions implicated in executive functioning and attentional tasks, caudate and total brain volumes were examined in boys with attention deficit hyperactivity disorder (ADHD) and normal comparison subjects. To gain developmental perspective, a wide range was sampled for both groups. Method: The brains of 50 male ADHD patients (aged 6-19) and 48 matched comparison subjects were scanned by magnetic resonance imaging (MRI). Volumetric measures of the head and body of the caudate nucleus were obtained from T 1 -weighted coronal images

Quantitative morphology of the caudate nucleus in attention deficit hyperactivity disorder.

Objective: By means of quantitative neuroanatomic imaging the authors assessed the hypothesis that there are structural brain abnormalities relevant to frontal lobe circuitry in children with attention deficit hyperactivity disorder (ADHD). Method: The midsagittal cross-sectional area of the corpus callosum, divided into seven sections, was measured from magnetic resonance images of 1 8 boys with ADHD and 1 8 carefully matched normal boys. Results: Two anterior regions, the rostrum and the rostral body, were found to have significantly smaller areas in the ADHD group. These areas correlated in the expected direction with teacher and parent ratings of hyperactivity/impulsivity. Conclusions: This finding supports theories ofabnormal frontal lobe development and function in ADHD. (Am J Psychiatry 1994; 151:665-669)

F X Castellanos

Papers

Brain development during childhood and adolescence: a longitudinal MRI study.

Quantitative Brain Magnetic Resonance Imaging in Attention-Deficit Hyperactivity Disorder

Cerebellum in attention-deficit hyperactivity disorder: a morphometric MRI study.

Quantitative morphology of the caudate nucleus in attention deficit hyperactivity disorder.

Quantitative morphology of the corpus callosum in attention deficit hyperactivity disorder