Orbitofrontal connectivity with resting-state networks is associated with midbrain dopamine D3 receptor availability

Area of Science:

• Neuroscience
• Molecular Psychiatry
• Cognitive Neuroscience

Background:

• Dopamine D3 receptor (D3R) function is critical in neuropsychiatric disorders like addiction.
• Frontal cortical connectivity disruptions are implicated in these disorders.
• The link between molecular D3R markers and functional brain networks remains underexplored.

Purpose of the Study:

• To investigate the association between midbrain D3R availability and functional brain network interactions.
• To explore the relationship between D3R availability and connectivity in reward and cognitive processing regions.

Main Methods:

• Combined [(11)C]-(+)-PHNO positron emission tomography and resting-state functional magnetic resonance imaging in healthy individuals.
• Assessed midbrain D3R availability and functional connectivity between brain regions and networks.

Main Results:

• High midbrain D3R availability linked to reduced orbitofrontal cortex (OFC) connectivity with cognitive control and salience networks.
• Greater OFC connectivity with reward circuitry and default mode network observed in individuals with high D3R availability.
• Demonstrated differential interactions between OFC and key brain networks based on D3R availability.

Conclusions:

• Midbrain D3R availability is associated with distinct functional connectivity patterns in the OFC and related networks.
• Findings support dopamine D3R signaling as a key molecular pathway in goal-directed behavior.
• Highlights the interplay between molecular receptor availability and large-scale brain network function.