Abstract
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Objectives Selection of an appropriate response by inhibiting irrelevant options is an important function of the brain. This function is impaired in a number of conditions including ADHD. Since dopamine neurotransmission is dysregulated in these conditions, we examined its role in the processing of response inhibition using a dynamic molecular imaging technique.
Methods In this experiment healthy volunteers were asked to perform Eriksen’s flanker task after receiving a radiolabeled dopamine receptor ligand 11C-raclopride. In this task volunteers were shown a series of 7 arrowheads and asked to indicate the direction of the target arrowhead located in the center. In the control (congruent) condition all arrowheads pointed to the same direction while in the test (incongruent) condition the target and flanker arrowheads pointed to different directions. In the test condition volunteers were required to inhibit prepotent responses indicated by a majority of arrowheads (flankers). The inhibition was not needed in the control condition because all arrowheads pointed to the same direction. The control condition was started immediately after the ligand injection and after 25 min it was replaced by the test condition, which continued for 15 min. The PET data acquisition started immediately after the ligand injection in 30 and 60 sec frames.
Results The PET data, analyzed using modified version of the simplified reference region model, revealed that the ligand displaced from the receptor sites at significantly higher rate in the test condition. The increase was most significant in the left caudate but observed also in the putamen and right caudate. The ligand binding potential decreased significantly in the same areas indicating release of endogenous dopamine during task performance.
Conclusions The results suggest that response inhibition is controlled by striatal dopamine. The finding will help better understanding of the neuropathology of conditions in which inhibitory processes are impaired. This could lead to development of novel diagnostic and therapeutic strategies.
Research Support NIH grant 1R21MH07943