Relationship of self‐transcendence traits with in vivo dopamine D2/3 receptor availability and functional connectivity: An [¹⁸F]fallypride PET and fMRI study

Abstract

Genetic research has implicated dopamine neurotransmission in the expression of the self‐transcendence trait in humans. However, molecular imaging of dopaminergic markers is undocumented in relation to this personality trait. In this multimodal imaging study, we first investigated the relationship between the self‐transcendence trait and in vivo dopamine D2/3 receptor availability using [18F]fallypride positron emission tomography (PET). We next conducted seed‐based functional connectivity analyses using resting‐state functional magnetic resonance imaging (rs‐fMRI) data with regions derived from the PET analysis as seeds to explore the functional significance of D2/3 receptor availability foci associated with the self‐transcendence trait. Twenty‐one healthy subjects underwent high‐resolution PET with [18F]fallypride and a subset of 18 subjects also completed 3‐Tesla rs‐fMRI. The Temperament and Character Inventory was used to measure the self‐transcendence trait. A voxel‐based whole brain analysis revealed that the [18F]fallypride binding potential (BPND) within the cluster of the left insula was significantly positively correlated with self‐transcendence trait scores. A region‐of‐interest analysis also showed a significant positive correlation between self‐transcendence and [18F]fallypride BPND in the left insula. The exploratory [18F]fallypride BPND seed‐based rs‐fMRI analysis showed that the functional connectivity from the left insula seed to the prefrontal cortices (including the inferior frontal region) was negatively associated with self‐transcendence trait scores. The results of the present study suggest that D2/3 receptor‐mediated neurotransmission in the left insula may constitute a significant neurobiological factor in the self‐transcendence trait. The negative associations between BPND seed‐based functional connectivity and self‐transcendence trait scores may suggest reduced prefrontal control in this personality trait.

Advances in simultaneous PET/MR for imaging neuroreceptor function

“…100 In a separate study, increased connectivity between striatal and extrastriatal D 2 receptor availability was determined in patients with schizophrenia with a high-affinity radiotracer. 101 Whether the positive vs. negative correlations found in these studies are driven by excitatory vs. inhibitory dopamine projections, and correlate with behavioral measures, 102 is an intriguing area of research. Due to whole-brain coverage that both PET and fMRI can provide, comparing striatal vs. extrastriatal or excitatory vs. inhibitory dopaminergic and functional network modulations is an exciting research area that PET/MR can be used to expand to.…”