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Neural substrates, electrophysiological correlates and dopaminergic modulation of different forms of inhibition in humans

Final Activity Report Summary - INHIBITION (Neural substrates, electrophysiological correlates and dopaminergic modulation of different forms of inhibition in humans)

Malfunctioning of a part of the human brain called the fronto-striatal circuitry is thought to lead to a lack of inhibition and thereby to impulsivity, which plays a crucial role in attention deficit-hyperactivity disorder (ADHD) and drug addiction. Even though different forms of impulsivity exist, they have never been directly compared to investigate putative underlying differential activity in the fronto-striatal circuitry. Further, we were interested in the modulation of the fronto-striatal circuitry by signalling substances or neurotransmitters.

To investigate whether different forms of impulsivity would differentially recruit different parts of the fronto-striatal circuitry, we used event-related functional magnetic resonance imaging (fMRI), because it is a non-invasive technique with good spatial resolution. We found that two parts of the fronto-striatal circuitry, namely the right inferior frontal gyrus (IFG) and the pre supplementary motor area (preSMA) are differentially recruited, depending on the type of inhibition involved.

Further, we measured the effect of atomoxetine, a well-known reuptake inhibitor of the neurotransmitter noradrenaline on activity in the fronto-striatal circuitry. By inhibiting reuptake of noradrenaline, atomoxetine increases the brain levels of noradrenaline. We are currently analysing these fMRI data and hope to find out soon the effect of increased noradrenaline on the activity in the fronto-striatal circuitry.

A better understanding of the functioning and modulation of the fronto-striatal circuitry by neurotransmitters will advance not only the treatment development for and understanding of brain diseases like attention deficit hyperactivity disorder (ADHD) and drug addiction but also that of the usually well-functioning but sometimes impulsive brain.