Functional frontalisation with age: mapping neurodevelopmental trajectories with fMRI
Introduction
Attention deficit-hyperactivity disorder (ADHD) is a child psychiatric disorder characterised by inattention, hyperactivity and impulsivity [1]. The pathogenesis is likely to be developmental and the characteristic symptoms are commonly held to reflect deficits of higher order executive functions [2], [19]. Using functional magnetic resonance imaging (fMRI) we have recently shown reduced activation of frontal and other brain regions in adolescents with ADHD performing two executive functions: motor timing and motor response inhibition [20]. This finding of hypofrontality was interpreted as indicative of delayed maturation of frontal lobe function in the group of patients with ADHD.
In this study we wanted to investigate further our assumption that functional activation of the human frontal lobes, measured by fMRI, normally tends to increase with age as individuals mature from adolescence to early adulthood. If this were the case, it would support our interpretation of hypofrontality in ADHD as indicative of delayed or deviant brain maturation. The frontal lobes are among the last cortical regions to become anatomically and functionally mature, and this developmental process of frontalisation may not be completed until the mid-twenties or even later [11], [26], [27]. Dopaminergic projections to prefrontal cortex are thought to play an important role in neurogenesis [14], [22], and dysfunction of the mesoneocortical dopaminergic system [8] is one strand of evidence (among others reviewed by Swanson [24]) suggesting a neurodevelopmental model for the pathogenesis of ADHD.
Although it is widely recognised that fMRI offers many potential advantages for developmental neuroimaging in both normal and patient groups, there were no previously published fMRI data either for or against our initial hypothesis that the patterns of frontal activation induced by higher order motor control would show age related changes in normal subjects. We scanned a total of 17 healthy volunteers, nine adolescents and eight adults, under the same two experimental conditions (motor timing and motor response inhibition tasks) as previously reported in our case-control study of ADHD [20]. We tested the hypothesis of a group difference in functional brain activation and of a linear effect of age on power of this activation at both voxel and regional levels of analysis.
Section snippets
Subjects
Seventeen healthy right-handed male volunteers participated: age range 12–40 years, mean age=21.6, standard deviation (SD=8.45 years). This sample includes 9 normal adolescents previously reported (age range 12–19, mean age=15.01, SD=2.3 years) which were compared to 8 adults (age range 22–40; mean age=28.8, SD=6.64). No group differences were observed in a non-verbal intelligence measure [17]. For comparative purpose, fMRI data for 7 right-handed, clinically referred and unmedicated
Stop task
No differences were observed between adults and adolescents in mean reaction time to airplanes (mean reaction time for adults: 631.6 ms, mean reaction time for adolescents: 664.2 ms; SD=66.4 ms, t=0.71; df=15, P=0.5) or percentage of correctly inhibited responses following presentation of a bomb (adults: 93.1%, SD=7.5%; adolescents 93.4% SD=4.9%, t=0.07, There was no significant correlation between percentage of correctly inhibited responses and age (r=0.09, df=15, P
Discussion
The main findings of this study support our hypothetical expectation that power of functional activation of frontal cortex would normally increase over the age-range of adolescence and adulthood.
In the delay task, which adults performed better than adolescents, there was an increase in power of activation in adults compared to adolescents in a fronto-striato-parietal network. Most of the brain regions showing a significant group difference in mean power of response also demonstrated a
Acknowledgements
This work was supported by the European BIOPHYRIS network and by the Bethlem and Maudsley Research Fund (BMRF). S.O. was supported by a European Fellowship from the European Union Programme for the Training and Mobility of Researchers. E.B. is supported by the Wellcome Trust. The data have been previously presented at the Internet World Congress of Biomedical Sciences (INABIS), McMasters University, Toronto, Canada, 1998, invited abstract for symposium on ADHD, 0538 and in abstract form
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