Frontal and temporal dopamine release during working memory and attention tasks in healthy humans: a positron emission tomography study using the high-affinity dopamine D2 receptor ligand [11C]FLB 457

Abstract

Experimental studies on animals have shown that dopamine is a key neurotransmitter in the regulation of working memory (WM) functions in the prefrontal cortex. In humans, blood flow studies show prefrontal involvement in WM functions, but direct evidence for the involvement of the dopaminergic system in WM is lacking. Using positron emission tomography with a recently developed high-affinity dopamine D2 receptor tracer, [11C]FLB 457, we explored frontal, temporal, and parietal D2 receptor availability in 12 healthy volunteers while they were performing verbal WM and sustained attention tasks. During the performance of both tasks, reduced D2 receptor availability was observed in the left ventral anterior cingulate, suggesting an attention or arousal-related increase in dopamine release during these tasks. Compared with the sustained attention task, the verbal WM task reduced D2 receptor availability in the ventrolateral frontal cortex bilaterally and in the left medial temporal structures (amygdala, hippocampus), suggesting that dopamine release in these regions might have a specific role in WM. In addition, correlation analyses indicated that increased dopamine release in the right ventrolateral frontal cortex and the left ventral anterior cingulate during the WM task was associated with faster and more stable WM performance, respectively. Our results indicate that regionally specific components of the frontotemporal dopaminergic network are functionally involved in WM performance in humans.

Figure 1.

Visualization of the size, shape, and localization of the ROIs. vAC, Ventral AC; dAC, dorsal AC; Cer, cerebellum.

Figure 2.

Mean ± SEM reaction-time graphs for the vigilance and working memory tasks. Each time section represents a block of 90 stimuli. Reaction times and related SDs remained fairly stable during both tasks, although each task took ∼70 min.

Figure 3.

Individual BP values of [¹¹C]FLB 457 related to working memory-specific findings. Individual BP values in the ventrolateral frontal cortex and in the left medial temporal lobe during the vigilance and WM conditions are presented.

Figure 4.

Visualization of a voxel-based statistical analysis. Compared with the vigilance task, the BP of [¹¹C]FLB 457 decreased during the working memory task bilaterally in the VLFC (left, p = 0.008; right, p = 0.02) (A-C) and in the left medial temporal lobe (p < 0.01) (D). Compared with the resting state baseline, both the vigilance task (p = 0.001) (E) and the working memory task (p < 0.001) (F) induced a decrease in the BP of [¹¹C]FLB 457 in the left ventral AC. All p values have been corrected for multiple comparisons. The results are visualized on a brain model (top) and on an average MRI template image (bottom) and presented in line with the neurological convention (right is right).