Impulsiveness as a timing disturbance: neurocognitive abnormalities in attention-deficit hyperactivity disorder during temporal processes and normalization with methylphenidate

Abstract

We argue that impulsiveness is characterized by compromised timing functions such as premature motor timing, decreased tolerance to delays, poor temporal foresight and steeper temporal discounting. A model illustration for the association between impulsiveness and timing deficits is the impulsiveness disorder of attention-deficit hyperactivity disorder (ADHD). Children with ADHD have deficits in timing processes of several temporal domains and the neural substrates of these compromised timing functions are strikingly similar to the neuropathology of ADHD. We review our published and present novel functional magnetic resonance imaging data to demonstrate that ADHD children show dysfunctions in key timing regions of prefrontal, cingulate, striatal and cerebellar location during temporal processes of several time domains including time discrimination of milliseconds, motor timing to seconds and temporal discounting of longer time intervals. Given that impulsiveness, timing abnormalities and more specifically ADHD have been related to dopamine dysregulation, we tested for and demonstrated a normalization effect of all brain dysfunctions in ADHD children during time discrimination with the dopamine agonist and treatment of choice, methylphenidate. This review together with the new empirical findings demonstrates that neurocognitive dysfunctions in temporal processes are crucial to the impulsiveness disorder of ADHD and provides first evidence for normalization with a dopamine reuptake inhibitor.

Figure 1

ANOVA between-group differences showing reduced brain activation in ADHD boys compared with healthy comparison boys. (a) Motor timing of 5 s, seven boys with ADHD compared with nine healthy controls during a sensorimotor synchronization task to a 5 s interval (Rubia et al. 1999b); (b) temporal discrimination of hundreds of millisecond differences, 21 medication-naive ADHD boys compared with 17 healthy controls during temporal discrimination of intervals that differed by hundreds of milliseconds (Smith et al. 2008); and (c) temporal discounting of a week, month and year, 10 boys with ADHD compared with 10 healthy controls during a temporal discounting task of weeks to a year.

Figure 2

Within-group brain activation maps for the contrast of temporal discrimination versus order attribution task at p<0.05 for voxel and p<0.01 at cluster levels for (a) 12 healthy controls; and 12 medication-naive patients with ADHD under either (b) the placebo, or (c) the medication conditions.

Figure 3

Within-group ANOVA comparing medication status for the time discrimination two-order attribution contrast at p<0.05 for voxel and p<0.01 for cluster levels. More lenient effects of MPH compared with placebo are also shown at p<0.05. (a) MPH>placebo and (b) placebo<MPH.

Figure 4

Case-control ANOVAs comparing healthy controls with ADHD boys for the contrast of time discrimination versus order attribution task during either the (a) placebo condition ((i) controls>ADHD and (ii) ADHD>controls) or (b) the medication condition (MPH) at p<0.05 for voxel and p<0.006 for cluster comparisons. Differences at more lenient p-values of <0.05 at cluster levels are shown in (a).