Abstract
INTRODUCTION: Nicotine addiction, a multifaceted neuropsychiatric disorder, profoundly impacts brain functions through interactions with neural pathways. Despite its significance, the impact of tobacco smoking on the whole-brain functional connectome remains largely unexplored. AIMS AND METHODS: We conducted a whole-brain analysis on 24 539 adults aged 40 and above from the United Kingdom Biobank cohort. Subjects were categorized into individuals who use nicotine and those who do not use nicotine based on current and chronic tobacco smoking information. Functional connectivity was assessed using resting-state functional magnetic resonance imaging. We employed a network analysis method to assess the systematic effects of tobacco smoking on brain connectome by identifying subnetworks that show nicotine-use-related differences. RESULTS: Our analyses revealed two nicotine-use-related subnetworks with distinct network structure (permutation p < .001). In the first network, there is a significant decrease in resting-state functional connectivity (rsFC) between the basal ganglia regions (eg, nucleus accumbens) and 73% of the remaining brain regions, emphasizing the central hub role of basal ganglia in addictive smoking behaviors. Additionally, a data-driven subnetwork, mainly involving regions from frontal and occipital lobes, showed reduced rsFC among individuals who use nicotine. CONCLUSIONS: The results suggest significant alterations in the communication and coordination among the basal ganglia and the broader network of brain regions. The observed changes in rsFC indicate a widespread disruption in the connectivity patterns associated with nicotine use. IMPLICATIONS: This study identifies rsFC subnetworks related to chronic nicotine use through whole-brain connectome analysis. The findings confirm that widespread alterations in rsFC are centered around hub nodes within the basal ganglia, including bilateral nucleus accumbens, putamen, caudate, and globus pallidus. In addition, our analysis found a clique-forming subnetwork vulnerable to tobacco smoking consisting of regions from the visual, dorsal/ventral attention, and frontoparietal networks.