Imaging dopamine neurotransmission in live human brain

Abstract

Dopamine is an important regulator of cognition and behavior, but its precise influence on human brain processing remains unclear because of the lack of a reliable technique to study dopamine in the live human brain. In the recent years, a number of techniques have been developed to detect, map, and measure dopamine released during task performance. Most of these techniques are based on molecular imaging methods and have varying degrees of sensitivity. We developed a single-scan dynamic molecular imaging technique for the detection of dopamine released during task performance in the live human brain. This technique is extremely sensitive and has test-retest reliability. Using this technique, we detected dopamine released during the processing of a number of cognitive, behavioral, and emotional tasks. Since this technique acquires data that cannot be obtained using any other techniques, it extends the scope of neuroimaging research.

Keywords: attention-deficit hyperactivity disorder; behavior; cognition; dopamine; emotion; fallypride; molecular imaging; raclopride.

FIGURE 1

A schematic diagram of the three-compartment model.

FIGURE 2

Emotional processing in healthy volunteers: dopamine was released in the amygdala (A) and medial temporal lobe (B) during emotional processing. The figures show t-maps of the rate of ligand (¹⁸F-fallypride) displacement before and after task initiation. Maps are superimposed on mean PET images and represent changes across volunteers. The time–activity curve shows the concentration history (circles) and least square fits (solid line) for the ligand in the activated regions. There was a significant increase in the rate of ligand displacement after task was initiated (vertical line). The ligand concentration is expressed as kBq/cm².

FIGURE 3

Response inhibition in healthy volunteers: The striatal areas where the rate of ligand displacement increased significantly during inhibition of unwanted responses (in the incongruent condition of Eriksen’s flanker task) are shown on the t-map. The most significant increase was observed on the dorsal aspect of the body of the left caudate. The time–activity curves show the ligand concentration (open circles) and least square fit (solid lines) in a striatal area (upper curve) and in the reference region (lower curves). The data on the left of the vertical lines were acquired during the control task (congruent condition) and those on the right were obtained during response inhibition (incongruent condition). Significant reduction in ligand concentration after initiation of the inhibition task (incongruent condition) suggests increased rate of ligand displacement during task performance. The increase was due to competitive displacement induced by endogenous dopamine release. There was no significant change in the rate of ligand displacement in the reference region (cerebellum). This analysis used the linear extension of reference region tissue model (LE-SRRM).

FIGURE 4

Response inhibition in healthy volunteers: The t-maps generated using extended simplified reference tissue model (E-SRTM) show striatal areas where the ligand binding potential decreased significantly during inhibition of unwanted responses (incongruent condition of Eriksen’s flanker task) in comparison with the control condition (congruent condition of the Eriksen’s flanker task). It was most significant in the left caudate and putamen. These areas are located in close proximity to the areas where increased rate of ligand displacement was observed in the experiment (Fig. 3). An agreement in the data computed using two different receptor kinetic models significantly enhances the reliability of detection.