Atypical brain function in attention-deficit/hyperactivity disorder (ADHD) has been identified using both task-activation and functional connectivity fMRI approaches. Recent work highlights the potential for another measure derived from functional neuroimaging data, brain signal variability, to reveal insights into clinical conditions. Higher brain signal variability has previously been linked with optimal behavioral performance. At present, little is known regarding the relationship between resting-state brain signal variability and ADHD symptom severity. The current study examined the relationship between a measure of moment-to-moment brain (...) signal variability called mean-square successive difference (MSSD) and ADHD symptomatology in a group of children (7–12 years old) with ( n = 40) and without ( n = 30) a formal diagnosis of ADHD. A categorical analysis comparing subjects with and without a clinical diagnosis of ADHD showed no differences in MSSD between groups. A dimensional analysis revealed a positive relationship between MSSD and overall ADHD symptom severity and inattention across children with and without an ADHD diagnosis. Specifically, this positive relationship was found in medial prefrontal areas comprising the default mode network. These results demonstrate a link between intrinsic brain signal variability and ADHD symptom severity that cuts across diagnostic categories, and point to a locus of dysfunction consistent with previous neuroimaging literature. (shrink)

For decades, psychostimulants have been the gold standard pharmaceutical treatment for attention-deficit/hyperactivity disorder (ADHD). In the United States, an astounding 9% of all boys and 4% of girls will be prescribed stimulant drugs at some point during their childhood. Recent meta-analyses have revealed that individuals with ADHD have reduced brain volume loss later in life (>60 y.o.) compared to the normal aging brain, which suggests that either ADHD or its treatment may be neuroprotective. Crucially, these neuroprotective effects were significant in (...) brain regions (e.g., hippocampus, amygdala) where severe volume loss is linked to cognitive impairment and Alzheimer’s disease. Historically, the ADHD diagnosis and its pharmacotherapy came about nearly simultaneously, making it difficult to evaluate their effects in isolation. Certain evidence suggests that psychostimulants may normalize structural brain changes typically observed in the ADHD brain. If ADHD itself is neuroprotective, perhaps exercising the brain, then psychostimulants may not be recommended across the lifespan. Alternatively, if stimulant drugs are neuroprotective, then this class of medications may warrant further investigation for their therapeutic effects. Here, we take a bottom-up holistic approach to review the psychopharmacology of ADHD in the context of recent models of attention. We suggest that future studies are greatly needed to better appreciate the interactions amongst an ADHD diagnosis, stimulant treatment across the lifespan, and structure-function alterations in the aging brain. (shrink)