Nicotine beliefs elicit dose-response reactions in human brains

By Pooja Toshniwal PahariaReviewed by Benedette Cuffari, M.Sc.Jan 10 2024

In a recent study published in Nature Mental Health, researchers investigate whether nicotine-related beliefs may influence brain processes in a dose-dependent manner similar to pharmaceutical effects.

Study: Nicotine-related beliefs induce dose-dependent responses in the human brain. Image Credit: dore art / Shutterstock.com

Human beliefs and substance use

The precise mapping between personal beliefs and neurological substrates is unclear, which complicates our understanding of certain disorders like drug addiction. Understanding the influence of attitudes and expectations on pharmacological treatments, in which individual medication responses vary greatly, requires elucidating these brain systems. The dose-response connection is fundamental to pharmaceutical studies; however, it has received less attention in neuroscience studies of human beliefs.

About the study

In the present study, researchers assess the influence of nicotine dose perceptions on the human brain, using nicotine as a test case.

Previous studies have reported that assumptions related to nicotine strength in electronic cigarettes can alter thalamus activity and ventromedial prefrontal cortex (vmPFC) functional connectivity. Therefore, in the present study, participants were told to believe that the nicotine levels in electronic cigarettes was low, medium, or high, with nicotine concentrations remaining constant. Healthy non-smokers were also included as controls.  

All study participants underwent functional magnetic resonance imaging (fMRI) and completed a decision-making task known to involve nicotine-affected brain networks. Study participants were also assigned a value-based decision-making assignment, during which they had to place positive and negative bets.

Nicotine attitudes were hypothesized to alter brain activity in a way comparable to pharmacological dose-dependent responses. More specifically, nicotine dose-related thoughts were predicted to influence thalamic activity and functional coupling in the vmPFC, thus underscoring the significance of beliefs in modulating nicotine-induced responses.

A non-parametric technique was applied to confirm the association between beliefs and brain activity. To further understand the impact of nicotine on belief manipulation, an additional study was conducted with nicotine-dependent adult volunteers from the Dallas-Fort Worth area, including individuals who had never vaped before.

Cotinine, which is the primary metabolite of nicotine, was measured in saliva samples by high-performance liquid chromatography (HPLC) and mass spectrometry (MS). The United States Food and Drug Administration (FDA) May 2018 Guidance for Industry on Bioanalytical Method Validation was utilized to validate the cotinine detection techniques.

Study findings

Nicotine strength beliefs elicited dose-dependent responses by the thalamic region, a critical nicotine binding site. Nicotine-associated beliefs also altered the thalamic-vmPFC connection.

The perceived nicotine intensity of participants rose considerably as a function of their informed views about nicotine dose. However, there was no effect on nicotine intake, metabolism, or saturation.

Changes in cotinine concentrations caused by vaping were comparable across situations. This suggests that nicotine metabolism was unlikely to be a factor leading to any brain-based abnormalities.

Baseline carbon monoxide (CO) and desire levels were comparable across situations, thus indicating that education affected participant views about nicotine strength. Value-related thalamic activities responded to instructional attitudes about nicotine strength in a dose-dependent way.

No other brain areas exhibited comparable patterns in response to beliefs with the same statistical threshold. An independent anatomical mask was used for an area of interest (ROI) analysis, in which blood-oxygen-level-dependent (BOLD) signals from the thalamus were discriminated between taught belief conditions.

The allocation of belief conditions had much higher beta estimates than the surrogate distribution. Moreover, a 49% accuracy in decoding the taught belief condition from dispersed multivoxel patterns of thalamic activity was achieved, which was much higher than the chance level of 33%.

Subjective assessments of perceived nicotine intensity were associated with reward-related thalamic activities. Thus, subjective beliefs influenced by nicotine dosage instructions elicited dose-based thalamic responses. Nicotine beliefs did not affect reward-related striatal activity; however, these beliefs influenced the prefrontal-thalamic functional connection, as the ventral striatum monitored the value signal.

Nicotine beliefs impacted the functional association between the vmPFC and thalamus at the whole brain level and by ROI analysis. Comparatively, a different set of psychophysiological interaction (PPI) studies utilizing the ventral striatal region as the seed location did not reveal any significant alterations in functional relationships. Nicotine-related perceptions affected both thalamic activity and the prefrontal-thalamic connection in a dose-dependent manner.

Conclusions

Beliefs have a vital function in the brain, especially in addiction. In the current study, nicotine dose instructions affected users' perceptions of nicotine potency in e-cigarettes. These beliefs also influenced thalamic activity and functional connectivity in the prefrontal cortex-thalamus circuit.

The thalamic region, which is abundant in neuronal nicotinic acetylcholine receptors (nAChRs), is responsible for the attention-improving effects of nicotine. The vmPFC-thalamus circuit contains parametric data on beliefs and expectations, thus emphasizing their significance in abstract mental states. Nicotine-related thoughts also caused dose-based responses by the thalamus, which is a significant nicotine-binding site.