Smoking and High-Altitude Exposure Affect Intrinsic Neural Activity: A fMRI Study of Interactive Effects

Abstract

Smoking and high-altitude (HA) exposure both adversely affect human health, with smoking linked to various cancers and high-altitude environments causing physiological and neurological changes. Although the effects of smoking and HA exposure on brain structure and function have been studied separately, their combined impact is still rarely explored. This study aims to investigate the interactive effects of smoking and HA exposure on intrinsic brain activity using the resting-state functional magnetic resonance imaging (rs-fMRI) analysed by the amplitude of low-frequency fluctuations (ALFF) method. We used a mixed sample design, including four groups: (i) HA smokers (n = 22); (ii) HA nonsmokers (n = 22); (iii) sea-level (SL) smokers (n = 26); and (iv) SL nonsmokers (n = 26), for a total of 96 male participants. All subjects underwent resting-state functional magnetic resonance imaging. ALFF was used to assess differences in brain activity among the four groups. Two-way analysis of variance (ANOVA) was conducted to analyse the effects of smoking, high-altitude exposure and their interaction on ALFF. As for the main effect of smoking, elevated ALFF was found in the right superior frontal gyrus, right middle frontal gyrus, right inferior frontal gyrus, right middle cingulate cortex and right precentral gyrus. As for the main effect of HA exposure, elevated ALFF was found in the right putamen, right insula, right inferior frontal gyrus, right middle temporal gyrus, right precentral gyrus, right inferior temporal gyrus and right fusiform. A significant interaction effect between smoking and HA exposure was observed in the right precentral gyrus. Post hoc analysis for the right precentral gyrus showed significantly increased ALFF in groups including HA versus SL smokers; HA versus SL nonsmokers; and HA smokers versus HA nonsmokers. Our findings demonstrate that both smoking and HA exposure independently influence spontaneous brain activity, with a significant interaction between the two factors in modulating brain function. These results offer a neuroimaging-based perspective on substance addiction in high-altitude populations and contribute to a deeper understanding of high-altitude adaptation.

Keywords: amplitude of low‐frequency fluctuation; high‐altitude exposure; interactive effect; nicotine addiction; resting‐state functional magnetic resonance imaging; smoking.

FIGURE 1

The main effects of HA and smoking. (a) The main effects of smoking, GRF corrected, p voxel < 0.005 and p cluster < 0.05; (b) the main effects of HA, GRF corrected, p _FWE voxel < 0.001, p cluster < 0.05 and cluster size > 100. ‘R’ means the side is to the right.

FIGURE 2

The interaction effect of smoking and HA. (a) A significant interaction effect shown by ALFF in right precentral gyrus using two‐way ANOVA (GRF corrected, p voxel < 0.005 and p cluster < 0.05). (b, c) Planned post hoc analysis of the right precentral gyrus among the four groups. The vertical bar indicates the maximum and minimum across subjects. ****p < 0.0001, **p < 0.01, ^ns p > 0.05. HA‐SM, high‐altitude smokers; HA‐NSM, high‐altitude nonsmokers; SL‐NSM, sea‐level nonsmokers; SL‐SM, sea‐level smokers.

FIGURE 3

The ALFF values in the right precentral gyrus are correlated with FTND in the HA‐SM group.