Brain 5-HT2A receptor binding and its neural network related to behavioral inhibition system

Kazuho Kojima,Shigeki Hirano,Tetsuya Suhara,Keisuke Takahata,Hiroki Hashimoto,Ming-Rong Zhang,Yoko Ikoma,Takehito Ito,Yasuyuki Kimura,Makiko Yamada,Hiroshi Ito,Satoshi Kuwabara,Keita Yokokawa,Kazunori Kawamura,Chie Seki,Makoto Higuchi

doi:10.1007/s11682-021-00609-2

Abstract

The tendency to avoid punishment, called behavioral inhibition system, is an essential aspect of motivational behavior. Behavioral inhibition system is related to negative affect, such as anxiety, depression and pain, but its neural basis has not yet been clarified. To clarify the association between individual variations in behavioral inhibition system and brain 5-HT2A receptor availability and specify which brain networks were involved in healthy male subjects, using [18F]altanserin positron emission tomography and resting-state functional magnetic resonance imaging. Behavioral inhibition system score negatively correlated with 5-HT2A receptor availability in anterior cingulate cortex. A statistical model indicated that the behavioral inhibition system score was associated with 5-HT2A receptor availability, which was mediated by the functional connectivity between anterior cingulate cortex and left middle frontal gyrus, both of which involved in the cognitive control of negative information processing. Individuals with high behavioral inhibition system displays low 5-HT2A receptor availability in anterior cingulate cortex and this cognitive control network links with prefrontal-cingulate integrity. These findings have implications for underlying the serotonergic basis of physiologies in aversion.

Highlights

The fundamental features of complex behavior have long been discussed as being categorizable into the approach to rewards and the avoidance of punishments
Regional 5‐HT2A receptor availability measured by [18F]altanserin positron emission tomography (PET)
Higher BPP was measured in the anterior cingulate cortex (ACC) and orbitofrontal cortex (OFC), while low BPP was observed in the amygdala

Summary

Introduction

The fundamental features of complex behavior have long been discussed as being categorizable into the approach to rewards and the avoidance of punishments. These two systems can be applied to account for personality and motivation (Davidson, 1994; Gray, 1982; Higgins et al, 1994), positing that there are independent sensitivity in the respective systems. Gray proposes two systems together with an additional one: Behavioral Approach System (BAS), Behavioral Inhibition System (BIS), and FightFlight System (FFS) (see revised version of RST(Gray & McNaughton, 2000)). BAS corresponds to impulsivity, drug addiction, and attention deficit hyperactivity disorder; BIS is a self-reported sensitivity to punishment related to anxiety, depression, and pain, and FFS is fear at the psychological and psychiatric level (Bijttebier et al, 2009; Corr, 2002, 2004; Jensen et al, 2016)

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