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

Objective

Malfunctioning of the fronto-striatal circuitry in the brain 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. Two main categories of inhibition can be distinguished: response (or action) inhibition and inhibition of goal directed behaviour.

Whereas the first category prevents motor impulsivity, the latter category represents cognitive control of the individual to follow his own recognized best interest. It is not known whether both forms of inhibition utilize the fronto-striatal brain circuitry to the same extent or not. Electrophysiological correlates of response inhibition have been shown but electrophysiological evidence of inhibition of goal directed behaviour is lacking.

Further, it is unknown whether the two forms of inhibition are to the same extent dependent on modulation by neurotransmitters such as dopamine. Knowledge about this would greatly facilitate the development of more selective and accurate treatment of ADHD patients. In the proposed research, event-related functional magnetic resonance imaging (fMRI) will be combined with event-related brain potentials (ERP) in healthy human volunteers.

We will investigate whether response inhibition and inhibition of goal directed behaviour differentially utilize the fronto-striatal circuitry or to what extent it differs and disentangle electrophysiological correlates that mediate the two forms of inhibition. Further, the dependence of these neural substrates on dopaminergic modulation will be investigated, by testing the effect of sulpiride on the two forms of inhibition using both fMRI an ERP.

As an eventual goal of the project, event-related fMRI will be used in adult ADHD patients to investigate putative differences between the patients and the healthy volunteers in the functioning and dopaminergic modulation of the neural substrates for the two forms of inhibition.

Call for proposal

FP6-2004-MOBILITY-5
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Funding Scheme

EIF - Marie Curie actions-Intra-European Fellowships
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Coordinator

THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
Address
The Old Schools, Trinity Street
Cambridge
United Kingdom