Nicotine-related beliefs induce dose-dependent responses in the human brain Summary Beliefs have a powerful influence on our behavior, but their neural mechanisms remain elusive. Here we investigated whether beliefs could affect brain activities in a manner similar to dose-dependent pharmacological effects. Nicotine-dependent humans were told that the nicotine concentration in an e-cigarette was "low," "medium," or "high ," while the nicotine content was kept constant. After vaping, participants underwent functional neuroimaging and performed a decision-making task involving neural circuits affected by nicotine. Beliefs about nicotine potency induced dose-dependent responses in the thalamus , a key binding site for nicotine, but not in other brain regions such as the striatum. Nicotine-related beliefs also parametrically modulated connectivity between the thalamus and the ventromedial prefrontal cortex, a region important for decision-making. These findings reveal a high level of precision in how beliefs influence the brain, offering mechanistic insights into humans’ heterogeneous responses to drugs and the critical role of beliefs in addiction. |
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Mount Sinai researchers have shown for the first time that a person’s drug-related beliefs can influence their own brain activity and behavioral responses in a way comparable to the dose-dependent effects of pharmacology.
The implications of the study, which focused squarely on beliefs about nicotine, are profound. They range from elucidating how the neural mechanisms underlying beliefs may play a key role in addiction to optimizing pharmacological and non-pharmacological treatments by harnessing the power of human beliefs. The study was published in the journal Nature Mental Health .
"Beliefs can have a powerful influence on our behavior, but their effects are considered imprecise and rarely examined using quantitative neuroscience methods," says Xiaosi Gu, PhD, associate professor of psychiatry and neuroscience at the Icahn School of Medicine at Mount Sinai and lead author of the study. "We set out to investigate whether human beliefs can modulate brain activities in a dose-dependent manner similar to what drugs do, and found a high level of precision in how beliefs can influence the human brain. This finding could be "Crucial to advancing our knowledge about the role of beliefs in addiction, as well as a wide range of disorders and their treatments."
To explore this dynamic, the Mount Sinai team, led by Ofer Perl, PhD, a postdoctoral fellow in Dr. Gu’s lab when the study was conducted, instructed nicotine-dependent participants to believe that an e-cigarette they were point of vaping contained low, medium or high concentrations of nicotine, when in reality the level remained constant. Participants then underwent functional neuroimaging (fMRI) while performing a decision-making task involving neural circuits activated by nicotine.
The scientists found that the thalamus , a major nicotine binding site in the brain, showed a dose-dependent response to the subject’s beliefs about nicotine’s potency, providing compelling evidence to support the relationship between subjective beliefs and biological substrates in the human brain. This effect was previously thought to apply only to pharmacological agents. A similar dose-dependent effect of beliefs was also found in functional connectivity between the thalamus and the ventromedial prefrontal cortex, a brain region thought to be important for decision-making and belief states.
"Our findings provide a mechanistic explanation for the known variations in individual responses to drugs," notes Dr. Gu, "and suggest that subjective beliefs could be a direct target for the treatment of substance use disorders. They also "could improve our understanding of how cognitive interventions, such as psychotherapy, work at a general neurobiological level for a wide range of psychiatric conditions beyond addiction."
Dr. Gu, one of the world’s leading researchers in the emerging field of computational psychiatry , cites another way her team’s research could inform clinical care. "The finding that human beliefs about drugs play such a fundamental role suggests that we could potentially improve patients’ responses to drug treatments by harnessing these beliefs ," she explains.
Significantly, the Mount Sinai team’s work can also be seen in a much broader context: systematically harnessing beliefs to better serve mental health treatment and research in general.
"We are interested in testing the effects of drug beliefs beyond nicotine to include addictive substances such as cannabis and alcohol, and therapeutic agents such as antidepressants and psychedelics," says Dr. Gu. "It would be fascinating to examine, for example, how the potency of a drug might affect the effect of drug-related beliefs on the brain and behavior, and how long-lasting the impact of those beliefs might be. Our findings could potentially revolutionize how "We look at medications and therapy in a much broader health context."
