Meta-analysis of fMRI studies of timing in attention-deficit hyperactivity disorder (ADHD)

Attention-deficit hyperactivity disorder (ADHD) is associated with deficits in timing functions with, however, inconclusive findings on the underlying neurofunctional deficits. We therefore conducted a meta-analysis of 11 functional magnetic resonance imaging (fMRI) studies of timing in ADHD, comprising 150 patients and 145 healthy controls. Peak coordinates were extracted from significant case-control activation differences as well as demographic, clinical, and methodological variables. In addition, meta-regression analyses were used to explore medication effects. The most consistent deficits in ADHD patients relative to controls were reduced activation in typical areas of timing such as left inferior prefrontal cortex (IFC)/insula, cerebellum, and left inferior parietal lobe. The findings of left fronto-parieto-cerebellar deficits during timing functions contrast with well documented right fronto-striatal dysfunctions for inhibitory and attention functions, suggesting cognitive domain-specific neurofunctional deficits in ADHD. The meta-regression analysis showed that right dorsolateral prefrontal cortex (DLPFC) activation was reduced in medication-naïve patients but normal in long-term stimulant medicated patients relative to controls, suggesting potential normalization effects on the function of this prefrontal region with long-term psychostimulant treatment.