INHIBITION · Neural substrates, electrophysiological correlates and dopaminergic modulation of different forms of inhibition in humans
FP6 — Marie Curie Actions (Human Resources and Mobility)
- Duration
- 2006-01-01 → 2007-12-31
- EU contribution
- €167,665
- Participants
- 1
- Scheme
- EIF
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Results in brief
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.
Data: CORDIS, © European Union
Project 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.
Original text from CORDIS.
Participants
- University of Cambridge · CambridgeCoordinatorUnited Kingdom
Links
Data: CORDIS, © European Union