Metabolic Dynamics in the Prefrontal Cortex during a Working Memory Task in Young Adult Smokers

Abstract

<b><i>Introduction:</i></b> Cigarette smoking is known to modulate brain metabolism and brain function. How the dynamics of these metabolic alterations influence the active performance of higher order cognitive tasks in smokers, compared to non-smokers, is still unclear. The present exploratory study sought to examine the impact of smoking on the “complete” metabolic profile while the participants performed a working memory (N-back) task. <b><i>Methods:</i></b> The study sample consisted of 40 young male healthy participants (smokers [<i>n</i> = 20] and non-smokers [<i>n</i> = 20]). Functional magnetic resonance spectroscopy data were acquired using a 3 T whole-body MR system. Data analysis was performed using Java-based Magnetic Resonance User Interface software, and metabolite ratios with respect to creatine (Cr) were calculated. <b><i>Results:</i></b> On a behavioural level, smokers showed worse performance (measured by d’) than non-smokers. However, we observed significant differences in the metabolite concentrations in smokers compared to non-smokers, which also changed over the course of the N-back task. A significant effect of the group was observed with smokers showing lower glutamate/Cr (Glx/Cr) and choline/Cr (Cho/Cr) ratios than non-smokers. Further, N-acetyl aspartate (NAA/Cr) and Cho/Cr ratios were significantly different during the rest and the task conditions. In addition, our results demonstrated the metabolite interactions (NAA and Cho, Glx and myo-inositol [mI], and Cho and mI). <b><i>Conclusion:</i></b> Further studies are necessary to shed more light on the association between smoking behaviours and metabolic alterations. However, our preliminary findings would assist in this future research to have a complete understanding of the metabolite interactions not only in smoking but also in addiction research.

Changes in aspartate metabolism in the medial‐prefrontal cortex of nicotine addicts based on J‐edited magnetic resonance spectroscopy

“…Asp levels can induce severe neuroinflammatory processes and cell death (Boccella et al, 2015;Nuzzo, Feligioni, et al, 2019;Punzo et al, 2016). Our study found increased Asp levels in the mPFC of the brain of NAs, which we believe may be associated with the changes in the structure and cognitive functions of the mPFC as well as the addictive behavior (Bagga et al, 2021;Janes et al, 2016).…”

“…Our study not only found elevated levels of Asp in the prefrontal lobe of the brain in NAs, but also found that Asp was associated with daily nicotine intake in the correlation analysis. Therefore, we think that nicotine should be clearly In addition, the differences between the NAs and nonsmokers are not caused by one metabolite, but may also be caused by interactions between metabolites (Bagga et al, 2021;. Most previous studies have shown that NAA, Cr, mI, and Glu in the brain of NAs are significantly decreased, while Cho is significantly increased (Durazzo et al, 2016;Gallinat et al, 2007;Mennecke et al, 2014).…”

“…Meanwhile, they found that smokers displayed worse decision‐making and greater impulsivity. Bagga et al (2021) observed that smokers showed lower Glx/Cr and Cho/Cr ratios than nonsmokers in the PFC region. Their study also highlights that it is not one metabolite that underlies the significant differences in brain metabolism between smokers versus nonsmokers and different task conditions, but is the interplay between the metabolites (NAA and Cho, Glx and mI, and Cho and mI).…”

“…As known, nicotine addiction cannot only alter brain structure and function, but also cause changes in brain metabolism. Preceding MRS research on smoking has shown that nicotine can regulate biochemical metabolism in the brain, and NA is associated with changes in levels of regional metabolites containing NAA, cholinine (Cho), creatine (Cr), glutamate (Glu), and myo‐Inositol (mI) (Bagga et al, 2021; Durazzo et al, 2016; Gallinat et al, 2007; Li et al, 2018; Mennecke et al, 2014; O'Neill et al, 2014). The study by Mennecke et al (2014) showed that Glx (glutamate + glutamine) and Cho concentrations was remarkably increased in the left cingulate cortex in smokers relative to nonsmokers, and six out of seven smokers recovered normal Glx concentrations after quitting smoking, which proved that the physiological metabolism in human brain was related to nicotine addiction and withdrawal.…”

“…Therefore, PFC is considered to be one of the mostly abnormal brain regions involved in the formation of nicotine‐dependent behaviors. In addition, studies (Bagga et al, 2021; Durazzo et al, 2016) have shown that smoking is associated with metabolic abnormalities in the frontal lobe region of the brain.…”