A thalamic circuit represents dose-like responses induced by nicotine-related beliefs in human smokers

Could non-pharmacological constructs, such as beliefs, impact brain activities in a dose-dependent manner as drugs do? While beliefs shape many aspects of our behavior and wellbeing, the precise mapping between subjective beliefs and neural substrates remains elusive. Here, nicotine-addicted humans were instructed to think that an electronic cigarette (e-cigarette) contained either "low", "medium", or "high" levels of nicotine, while nicotine content was kept constant. After vaping the e-cigarette, participants performed a decision-making task known to engage neural circuits affected by nicotine while being scanned by fMRI. Activity in the thalamus, a key binding site for nicotine, increased parametrically according to belief dosage. Furthermore, the functional coupling between thalamus and ventromedial prefrontal cortex, a region implicated in value and state representations, also scaled to belief dosage. These findings illustrate a dose-dependent relationship between a thalamic circuit and nicotine-related beliefs in humans, a mechanism previously known to only apply to pharmacological agents.