Margaret Semrud-Clikeman

Volumetric MRI analysis comparing subjects having attention-deficit hyperactivity disorder with normal controls

Article abstract-Objective: To test by MRI-based morphometry the a priori hypotheses that developmental anomalies exist in attention-deficit hyperactivity disorder (ADHD) in left caudate and right prefrontal/frontal/ and/or posterior parietal hemispheric regions, in accord with neurochemical, neuronal circuitry and attentional network hypotheses, and prior imaging studies. Design: Case-control study. Setting: Academic medical center. Participants: Fifteen male subjects with ADHD without comorbid diagnoses (aged 12.4 +/- 3.4 years) and 15 male normal controls (aged 14.4 +/- 3.4), group-matched for age, IQ, and handedness. Main outcome measures: Global and hemispheric regional volumes (in cm3) of cerebral hemispheres, cortex, white matter, ventricles, caudate, lenticulate, central gray nuclei, insula, amygdala, and hippocampus. Results: Despite similar hemispheric volumes, ADHD subjects had smaller volumes of (1) left total caudate and caudate head (p < 0.04), with reversed asymmetry (p < 0.03); (2) right anterior-superior (frontal) region en bloc (p < 0.03) and white matter (p < 0.01); (3) bilateral anterior-inferior region en bloc (p < 0.04); and (4) bilateral retrocallosal (parietal-occipital) region white matter (p < 0.03). Possible structural correlates of ADHD response to stimulants were noted in an exploratory analysis, with the smallest and symmetric caudate, and smallest left anterior-superior cortex volumes found in the responders, but reversed caudate asymmetry and the smallest retrocallosal white matter volumes noted in the nonresponders. Conclusions: This study is the first to report localized hemispheric structural anomalies in ADHD, which are concordant with theoretical models of abnormal frontal-striatal and parietal function, and with possible differing morphologic substrates of response to stimulant medication. NEUROLOGY 1997;48: 589-601

Comorbidity between ADDH and Learning Disability: A Review and Report in a Clinically Referred Sample

A widely variable overlap ranging from 10 to 92% has been reported in the literature between attention deficit disorder with hyperactivity (ADDH) and learning disability (LD), most likely a result of inconsistencies in the criteria used to define LD in different studies. The following study seeks to more accurately determine rates of LD in clinically referred children. Using a psychometrically reliable methodological approach, it was expected that the rate of LD in ADDH children would be far more modest than previously reported. Subjects were referred children with ADDH (N = 60), children with academic problems (N = 30), and normal controls (N = 36) of both sexes with available psychological and achievement testing. Using a liberal definition of LD, significant differences were found between the groups (ADDH = 38% versus academic problems = 43% versus normals = 8%; p = 0.002). In contrast, more modest rates were found using two more stringent methods of assessment (23 and 17%; 10 and 3%; 2 and 0%, respectively; p = 0.02). Arithmetic-based LD appears to be equally identified by both stringent methods, whereas the liberal definition overidentified children in all three groups. These findings show that a liberal definition of LD overidentifies LD not only in ADDH children but also in normal children.

Corpus Callosum Morphology in Attention Deficit-Hyperactivity Disorder: Morphometric Analysis of MRI:

Although behavioral evidence provides support for the notion that attention deficit-hyperactivity disorder (ADHD) is related to central nervous system dysfunction, there is little direct evidence to reveal which neurometabolic systems or brain structures are involved. Recent magnetic resonance imaging (MRI) studies suggest that, compared to nondisabled controls, ADHD children may have a smaller right frontal region. Morphometric analysis of MRI scans was used in this exploratory study to determine whether correlated regional variation might exist in the corpus callosum of children with ADHD. While all MRI scans were judged to be clinically normal, morphometric analysis revealed that, compared to nondisabled controls, ADHD children had a smaller corpus callosum, particularly in the region of the genu and splenium, and in the area just anterior to the splenium. Interhemispheric fibers in these regions interconnect the left and right frontal, occipital, parietal, and posterior temporal regions. These results suggest that subtle differences may exist in the brains of children with ADHD and that deviations in normal corticogenesis may underlie the behavioral manifestations of this disorder.

Attention-deficit hyperactivity disorder: magnetic resonance imaging morphometric analysis of the corpus callosum.

OBJECTIVE The following study seeks to document possible differences in corpus callosal area and shape between children with attention-deficit hyperactivity disorder (ADHD) and controls. METHODS Fifteen carefully diagnosed right-handed male subjects with ADHD with overactivity symptomatology were compared to 15 right-handed male control subjects. The corpus callosum was divided into seven areas on the midsagittal slice of a magnetic resonance image with shape analysis also conducted. RESULTS An exploratory shape analysis showed no significant differences in shape between the groups. No group differences were found in the area, length, or anterior regions of the corpus callosum. The ADHD subjects were found to have significantly smaller posterior corpus callosum regions than the control group, with the splenium accounting for most of the variance between the groups. CONCLUSIONS The splenial area of the corpus callosum is smaller in children with ADHD than in a sample of normally developing children. These smaller areas may relate to commonly seen sustained attention deficits which in turn negatively impact on the development of more advanced levels of attention such as self-regulation. Further study of the regions surrounding the splenial area is suggested to determine whether they are correlated in size to the smaller corpus callosum.

Using MRI to Examine Brain-Behavior Relationships in Males With Attention Deficit Disorder With Hyperactivity

OBJECTIVE The relationship between neuropsychological measures of inhibition and sustained attention and structural brain differences in the regions of the caudate and the frontal region was examined in males with attention deficit disorder with hyperactivity (ADD/H). METHOD Ten males with ADD/H (aged 8-17) and 11 male controls (aged 9-18) participated in a neuropsychological evaluation and had a magnetic resonance imaging scan. RESULTS As had been reported previously by these authors, the children with ADD/H were found to have reversed asymmetry of the head of the caudate, smaller volume of the left caudate head, and smaller volume of the white matter of the right frontal lobe. Children with ADD/H were found to score more poorly on measures of inhibition and sustained attention but not on measures of IQ, achievement, or motor speed. Comparison of neuropsychological measures and brain structure measures indicated a significant relationship between reversed caudate asymmetry and measures of inhibition and externalizing behavior; i.e., children with reversed caudate asymmetry performed more poorly on measures of inhibition regardless of group membership. Poorer performance on sustained attention tasks was related to smaller volume of the right-hemispheric white matter. CONCLUSIONS There is emerging evidence that compromised brain morphology of selected regions is related to behavioral measures of inhibition and attention.

Dyslexia and brain morphology

Although the neurological basis of dyslexia has long been assumed, little direct evidence documents a relation between deviations in brain morphology and behavioral correlates of dyslexia. This article reviews two sources of evidence. Results of CT/MRI studies suggest that in the brains of dyslexics there is an increased incidence of symmetry in the region of the planum temporale and parietooccipital cortex that may be associated with language delay and handedness. Postmortem/cytoarchitectonic studies document symmetry of the plana, provide evidence of thalamic involvement, and chart widely distributed focal dysplasias preferentially involving the left frontal, left temporal, and right frontal regions. Methodological deficiencies characterize this literature, however, particularly regarding the diagnosis of dyslexia, appraisal of handedness and neurolinguistic deficits, and a failure to provide evidence that this pattern of involvement is unique to the dyslexic syndrome. These findings are discussed as they relate to neurobiological theory.

Right Hemispheric Dysfunction in Nonverbal Learning Disabilities: Social, Academic, and Adaptive Functioning in Adults and Children

This review addresses recent research on social and nonverbal learning disabilities. Involvement of right hemispheric dysfunction in these disabilities has been hypothesized, as studies with adults have suggested that documented right hemisphere damage may lead to deficits in social skills, prosody, spatial orientation, problem solving, and recognition of nonverbal cues. Studies of children purported to evidence nonverbal learning disabilities are reviewed and compared with the results from studies of adults with right hemisphere damage. Specific subtypes of nonverbal learning disabilities are reviewed, including the nonverbal perceptual-organization-output subtype, Aspergers Syndrome, Developmental Gerstmann Syndrome, left hemisyndrome, right hemisphere syndrome, and right parietal lobe syndrome. Finally, implications and future research needs are addressed. The need for a diagnostic nosology and improved and validated intervention techniques is stressed as is early identification of these types of specific nonverbal learning disabilities.

Rapid Naming Deficits in Children and Adolescents with Reading Disabilities and Attention Deficit Hyperactivity Disorder

Seventy-one children in three groups (reading disabilities, ADHD without reading disabilities, and normal controls) were compared on their ability to rapidly name colors, letters, numbers, and objects (RAN Tasks) and alternating letters/numbers and letters/numbers/colors (RAS tasks). Children with reading disabilities were found to be slower on letter- and number-naming tasks and made more errors on all tasks than controls or children with ADHD. There was an age effect for the RAN/RAS tasks, with younger children with reading disabilities performing more poorly on all tasks, while the older children with reading disabilities showed poorer performance only on the letter- and number-naming tasks.

Volumetric MRI differences in treatment-naïve vs chronically treated children with ADHD

Objective: To determine if there are differences in the volume of the caudate and anterior cingulate cortex (ACC) between children with attention deficit hyperactivity disorder (ADHD) and controls, and if such differences are related to the subjects’ history of stimulant treatment. Methods: We performed a case-control study in an academic medical center. Twenty-one healthy controls, 16 children with ADHD, combined type with a history of stimulant treatment, and 14 children with ADHD, combined type treatment naïve, underwent structural MRI. All children with ADHD were medication-free at the time of the MRI. Regional hemispheric volumes (in cm3) of caudate and anterior cingulate cortex were determined. Results: There were significant differences bilaterally on caudate volume for both ADHD groups vs controls, with no difference between the ADHD groups on either side. In contrast, the right ACC was significantly smaller for the ADHD-treatment naïve (ADHD/TN) group compared to the ADHD-treated (ADHD/Rx) and control group. The volume of left ACC approached significance contrast between ADHD/RX and ADHD/TN. There were no differences found between the ADHD/Rx and controls on the ACC volumes bilaterally. Conclusions: The results from this study indicate a relationship of previous treatment history with caudate and anterior cingulate volumetric changes in children with attention deficit hyperactivity disorder–combined type.

Critical Issues in Response-To-Intervention, Comprehensive Evaluation, and Specific Learning Disabilities Identification and Intervention: An Expert White Paper Consensus

Developed in concert with the Learning Disabilities Association of America (LDA), this White Paper regarding specific learning disabilities identification and intervention represents the expert consensus of 58 accomplished scholars in education, psychology, medicine, and the law. Survey responses and empirical evidence suggest that five conclusions are warranted: 1) The SLD definition should be maintained and the statutory requirements in SLD identification procedures should be strengthened; 2) neither ability-achievement discrepancy analysis nor failure to respond to intervention alone is sufficient for SLD identification; 3) a “third method” approach that identifies a pattern of psychological processing strengths and weaknesses, and achievement deficits consistent with this pattern of processing weaknesses, makes the most empirical and clinical sense; 4) an empirically-validated RTI model could be used to prevent learning problems, but comprehensive evaluations should occur for SLD identification purposes, and children with SLD need individualized interventions based on specific learning needs, not merely more intense interventions; and 5) assessment of cognitive and neuropsychological processes should be used for both SLD identification and intervention purposes.