Balancing risk-return decisions by manipulating the mesofrontal circuits in primates

Area of Science:

• Neuroscience
• Decision-making research
• Behavioral economics

Background:

• Decision-making involves inherent risk, with pathological risk-taking seen in gambling disorders.
• Understanding the neural mechanisms of risk assessment is crucial for addressing behavioral pathologies.

Purpose of the Study:

• To investigate the role of ventral Brodmann area 6 (area 6V) and its inputs from the ventral tegmental area (VTA) in modulating risk-dependent decision-making.
• To determine how specific VTA-to-area 6V pathways influence preferences for high-risk, high-return (HH) versus low-risk, low-return (LL) choices.

Main Methods:

• Utilized a high risk-high return (HH) versus low risk-low return (LL) choice task in macaque monkeys.
• Employed reversible pharmacological inactivation of area 6V.
• Used selective optogenetic activation of VTA projections to ventral and dorsal aspects of area 6V.
• Applied computational decoding to analyze behavioral modulations.

Main Results:

• Inactivation of area 6V impaired the dependency of decision-making on risk.
• Activation of the VTA pathway to the ventral aspect of area 6V increased preference for HH choices.
• Activation of the VTA pathway to the dorsal aspect of area 6V increased preference for LL choices.
• Computational decoding successfully captured these behavioral preference shifts.

Conclusions:

• Ventral tegmental area (VTA) inputs to area 6V are critical for regulating the balance between seeking high-risk, high-reward and low-risk, low-reward options.
• This pathway provides a neural basis for understanding and potentially modulating risk-taking behavior.