Familial vulnerability to ADHD affects activity in the cerebellum in addition to the prefrontal systems.
OBJECTIVE
Familial vulnerability to attention-deficit/hyperactivity disorder (ADHD) has been shown to be related to atypical prefrontal activity during cognitive control tasks. However, ADHD is associated with deficits in the cerebellum as well as deficits in frontostriatal circuitry and associated cognitive control. In this study, we investigated whether cerebellar systems are sensitive to familial risk for ADHD in addition to frontostriatal circuitry.


METHODS
We used an event-related, rapid mixed-trial functional magnetic resonance imaging design. The paradigm was a variation on a go/no-go task, with expected (go) and unexpected (no-go) events at expected and unexpected times. A total of 36 male children and adolescents completed the study, including 12 sibling pairs discordant for ADHD and 12 matched controls.


RESULTS
Children and adolescents with ADHD were less accurate on unexpected events than control subjects. Performance by unaffected siblings was intermediate, between that of children and adolescents with ADHD and controls. Functional neuroimaging results showed dissociation between activation in the cerebellum and anterior cingulate cortex: Activity in the anterior cingulate cortex was decreased for subjects with ADHD and their unaffected siblings compared with controls for manipulations of stimulus type (no-go trials), but not timing. In contrast, cerebellar activity was decreased for subjects with ADHD and their unaffected siblings for manipulations of timing, but not stimulus type.


CONCLUSIONS
These findings suggest that activity in both the prefrontal cortex and cerebellum is sensitive to familial vulnerability to ADHD. Unaffected siblings of individuals with ADHD show deficits similar to affected probands in prefrontal areas for unexpected events and in cerebellum for events atunexpected times.
Mulder
Martijn J
MJ
Drs. Mulder, van den Ban, van Engeland, and Durston are with the Department of Child and Adolescent Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht; Dr. Baeyens is with the Department of Psychology, Ghent University; Drs. Casey and Durston are with the Sackler Institute for Developmental Psychobiology; and Dr. Davidson is with the Department of Psychology, University of Massachusetts. Electronic address: m.mulder-7@umcutrecht.nl.
Baeyens
Dieter
D
Drs. Mulder, van den Ban, van Engeland, and Durston are with the Department of Child and Adolescent Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht; Dr. Baeyens is with the Department of Psychology, Ghent University; Drs. Casey and Durston are with the Sackler Institute for Developmental Psychobiology; and Dr. Davidson is with the Department of Psychology, University of Massachusetts.
Davidson
Matthew C
MC
Drs. Mulder, van den Ban, van Engeland, and Durston are with the Department of Child and Adolescent Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht; Dr. Baeyens is with the Department of Psychology, Ghent University; Drs. Casey and Durston are with the Sackler Institute for Developmental Psychobiology; and Dr. Davidson is with the Department of Psychology, University of Massachusetts.
Casey
B J
BJ
Drs. Mulder, van den Ban, van Engeland, and Durston are with the Department of Child and Adolescent Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht; Dr. Baeyens is with the Department of Psychology, Ghent University; Drs. Casey and Durston are with the Sackler Institute for Developmental Psychobiology; and Dr. Davidson is with the Department of Psychology, University of Massachusetts.
DEN Ban
Els VAN
EV
Drs. Mulder, van den Ban, van Engeland, and Durston are with the Department of Child and Adolescent Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht; Dr. Baeyens is with the Department of Psychology, Ghent University; Drs. Casey and Durston are with the Sackler Institute for Developmental Psychobiology; and Dr. Davidson is with the Department of Psychology, University of Massachusetts.
VAN Engeland
Herman
H
Drs. Mulder, van den Ban, van Engeland, and Durston are with the Department of Child and Adolescent Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht; Dr. Baeyens is with the Department of Psychology, Ghent University; Drs. Casey and Durston are with the Sackler Institute for Developmental Psychobiology; and Dr. Davidson is with the Department of Psychology, University of Massachusetts.
Durston
Sarah
S
Drs. Mulder, van den Ban, van Engeland, and Durston are with the Department of Child and Adolescent Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht; Dr. Baeyens is with the Department of Psychology, Ghent University; Drs. Casey and Durston are with the Sackler Institute for Developmental Psychobiology; and Dr. Davidson is with the Department of Psychology, University of Massachusetts.
D000293:Adolescent; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics* / Q000503:physiopathology; D001931:Brain Mapping; D002531:Cerebellum / Q000503:physiopathology*; D002648:Child; D003342:Corpus Striatum / Q000503:physiopathology*; D005838:Genotype; D006179:Gyrus Cinguli / Q000503:physiopathology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D021621:Imaging, Three-Dimensional; D008279:Magnetic Resonance Imaging; D008297:Male; D009415:Nerve Net / Q000503:physiopathology; D017397:Prefrontal Cortex / Q000503:physiopathology*; D018570:Risk Assessment