Research Identifies New Features Of Brain Structure That May Lead To ADHD

November 5, 2007
Research Conducted at the Kennedy Krieger Institute Takes New Approach to Studying Brain Basis of ADHD

(Baltimore, MD) - A study published today in Human Brain Mapping reveals an association between Attention Deficit Hyperactivity Disorder (ADHD) and a decrease in cortical volume, surface area and folding throughout the brain. Researchers from the Kennedy Krieger Institute in Baltimore, Md. found that children with ADHD showed decreased total brain volume and decreased volume throughout the cortex of the brain, the outer "grey matter" regions comprised of cells (neurons) of the brain. The findings further reveal that this reduction in cortical volume can be attributed to decreased folding in the cortex, suggesting that folding is the key structural brain feature associated with ADHD. This study, which is the first to examine cortical folding in ADHD, suggests that biological causes of ADHD may begin early in development, during gestation through infancy. This new research could help to identify key processes in the development of the brain that contribute to the disorder.

ADHD is a developmental disorder characterized by age-inappropriate inattentiveness, hyperactivity and impulsivity. It is estimated that approximately 2 million children are affected by ADHD, but despite its prevalence, there is a lack of understanding about the neurobiological basis of the disorder. While prior studies conducted have examined the brains of children with ADHD, most previous imaging studies have focused on measuring the size (volume) of brain regions. In this study, researchers went further by utilizing computer generated images, or "brain maps" for each subject that allowed them to examine and measure other important structural features, including surface area, thickness and folding throughout the brain as well as within specific regions. Investigators hypothesized that children with ADHD would show decreased cortical volume, thickness and surface area, with the greatest abnormality localized to the frontal lobes, important for control of attention and behavior.

The study found that children with ADHD showed a greater than 7 percent reduction in total cerebral volume (TCV) compared to the control group of typically developing children, which is consistent with previous research findings. Additionally, children with ADHD showed reduced cortical volumes and surface area of the brain compared to typically developing children, with a reduction of more than 8 percent in each brain hemisphere. As the study looked beyond just volume, additional measures of brain structure revealed that children with ADHD showed a significant decrease in cortical folding across the entire cerebral cortex, even after accounting for the decrease in TCV. No significant difference in thickness was detected. These results indicate that cortical folding is an important contributing factor to the reduced cortical volume observed in ADHD.

"These findings are an important step towards understanding the origin and development of ADHD, providing a clearer picture of the brain structure abnormalities associated with the disorder," said Dr. Stewart H. Mostofsky, senior study author and a pediatric neurologist in the Department of Developmental Cognitive Neurology at the Kennedy Krieger Institute. "Although the neurobiological basis of ADHD is yet to be established, our findings bring us one step closer to understanding how the disorder develops based on neurological features and not just the symptom profile."

Cortical folding begins in early development of the fetus (around 16 weeks of gestation) and reaches its peak around 18 months of age, which is followed by a gradual leveling out to adult levels at about 23 years of age. During development, when the cortex can no longer expand radially due to the size of the skull, the only way to increase the surface area is if the cortex becomes more folded. Cortical folding, therefore, is critical to increasing the structural and functional capacity of the brain.

Researchers examined children ages 8-12 years, including: 21 children with ADHD and a control group of 35 typically developing children who matched in age and gender. Participants were recruited from outpatient clinics at the Kennedy Krieger Institute, local area pediatricians, local chapters of Children and Adults with Attention Deficit Hyperactivity Disorder (CHADD) and through advertisements in the community. While many prior imaging studies have included children with ADHD who had other associated ("co-morbid") neuropsychiatric or developmental diagnoses, this study excluded children with ADHD who also had a history of other neuropsychiatric diagnoses including conduct disorder, mood disorder, generalized anxiety disorder, separation anxiety disorder and/or obsessive-compulsive disorder. Additionally, none of the children had a learning disability or a history of speech/language disorders.

In the future, Dr. Mostofsky and his colleagues hope to further examine the relevance and implications of cortical folding in ADHD and its potential applications for early diagnosis. Studies examining larger numbers of children will allow researchers to better understand the association between cortical folding and the behavioral features of ADHD. Furthermore, evaluating changes in cortical folding over extended periods of time, beginning in early childhood, will provide useful insight into the brain basis of the disorder.

About the Kennedy Krieger Institute

Internationally recognized for improving the lives of children and adolescents with disorders and injuries of the brain and spinal cord, the Kennedy Krieger Institute in Baltimore, MD serves more than 13,000 individuals each year through inpatient and outpatient clinics, home and community services and school-based programs. Kennedy Krieger provides a wide range of services for children with developmental concerns mild to severe, and is home to a team of investigators who are contributing to the understanding of how disorders develop while pioneering new interventions and earlier diagnosis. For more information on Kennedy Krieger Institute, visit www.kennedykrieger.org.