Stimulants alleviate information processing and task performance deficits in Attention
Deficit/Hyperactivity Disorder (ADHD). Long acting formulations of amphetamines such as
lisdexamphetamine dimesylate (LDX) are especially valuable as they target the school day and
improve classroom performance. Although stimulants have been widely used in treatment of
ADHD, the exact mechanism action and effect on task performance is not completely known.
According to the State Regulation Deficit (SRD) model, children with ADHD have difficulty
regulating their levels of arousal/activation during tasks in response to the changing
demands of the environment. This leads to problems with downregulating overaroused states and
upregulating underaroused states. According to this view, stimulants exert their therapeutic
effect (in part) by optimising arousal/activation levels - especially during states of
underarousal/activation. Arousal/activation levels can also be altered by extrinsic factors
such as event rate (ER), e.g., the rate at which information is presented. Multiple studies
suggest that very fast and very slow events can both cause problems for individuals with
ADHD, related to overarousal and underarousal state respectively. Putting these intrinsic
(stimulants) and extrinsic (ERs) factors together leads to the prediction that changing the
rate at which information is presented in a task may alter the efficacy of stimulants and
affect the optimal stimulant dose level. More specifically, one dose of stimulant that may be
optimal on slow ER tasks (as it increases arousal/activation level) may be less effective
under high ER tasks because in such a setting arousal/activation level needs to be lowered
and not increased further. Adding stimulants to an already overactivated state may exacerbate
the associated problems. The implication of this is that a different dose of stimulant will
be needed under different environmental conditions for optimal performance. For example,
children with ADHD might require different dosage in the classroom setting to optimize
performance. In addition, the neuropsychological basis of performance deficits and
improvement by ER and stimulants are also unclear. According to the SRD model, the underlying
mechanism can be specific problems in motor activation/preparation or effort regulation.
Event-related potentials (ERP), pupil size measurements and cardiac measures enable us to see
objectively how motor activation/preparation and effort are affected by ER and simulants.
In this study the investigators aim to test these predictions of the SRD model and identify
the neurobiological basis of stimulant action.
Phase:
Phase 3
Details
Lead Sponsor:
University Ghent
Collaborators:
Fund for Scientific Research, Flanders, Belgium Shire