Development of cortical asymmetry in typically developing children and its disruption in attention-deficit/hyperactivity disorder.
BACKGROUND
Just as typical development of anatomical asymmetries in the human brain has been linked with normal lateralization of motor and cognitive functions, disruption of asymmetry has been implicated in the pathogenesis of neurodevelopmental disorders such as attention-deficit/hyperactivity disorder (ADHD). No study has examined the development of cortical asymmetry using longitudinal neuroanatomical data.


OBJECTIVE
To delineate the development of cortical asymmetry in children with and without ADHD.


METHODS
Longitudinal study.


METHODS
Government Clinical Research Institute.


METHODS
A total of 218 children with ADHD and 358 typically developing children, from whom 1133 neuroanatomical magnetic resonance images were acquired prospectively.


METHODS
Cortical thickness was estimated at 40 962 homologous points in the left and right hemispheres, and the trajectory of change in asymmetry was defined using mixed-model regression.


RESULTS
In right-handed typically developing individuals, a mean (SE) increase in the relative thickness of the right orbitofrontal and inferior frontal cortex with age of 0.011 (0.0018) mm per year (t(337) = 6.2, P < .001) was balanced against a relative left-hemispheric increase in the occipital cortical regions of 0.013 (0.0015) mm per year (t(337) = 8.1, P < .001). Age-related change in asymmetry in non-right-handed typically developing individuals was less extensive and was localized to different cortical regions. In ADHD, the posterior component of this evolving asymmetry was intact, but the prefrontal component was lost.


CONCLUSIONS
These findings explain the way that, in typical development, the increased dimensions of the right frontal and left occipital cortical regions emerge in adulthood from the reversed pattern of childhood cortical asymmetries. Loss of the prefrontal component of this evolving asymmetry in ADHD is compatible with disruption of prefrontal function in the disorder and demonstrates the way that disruption of typical processes of asymmetry can inform our understanding of neurodevelopmental disorders.
Shaw
Philip
P
Child Psychiatry Branch, National Institute of Mental Health, Bethesda, MD 20892, USA. shawp@mail.nih.gov
Lalonde
Francois
F
Lepage
Claude
C
Rabin
Cara
C
Eckstrand
Kristen
K
Sharp
Wendy
W
Greenstein
Deanna
D
Evans
Alan
A
Giedd
J N
JN
Rapoport
Judith
J
D000293:Adolescent; D000328:Adult; D001289:Attention Deficit Disorder with Hyperactivity / Q000175:diagnosis / Q000473:pathology* / Q000503:physiopathology; D001921:Brain / Q000254:growth & development / Q000473:pathology / Q000503:physiopathology; D001931:Brain Mapping; D002540:Cerebral Cortex / Q000254:growth & development* / Q000473:pathology* / Q000503:physiopathology; D002648:Child; D002657:Child Development / Q000502:physiology*; D002675:Child, Preschool; D005625:Frontal Lobe / Q000254:growth & development / Q000473:pathology / Q000503:physiopathology; D007839:Functional Laterality / Q000502:physiology*; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D017397:Prefrontal Cortex / Q000473:pathology / Q000503:physiopathology; D011446:Prospective Studies