Functional Connectivity of the Raphe Nuclei: Link to Tobacco Withdrawal in Smokers

Faulkner, Paul; Ghahremani, Dara G.; Tyndale, Rachel F.; Hellemann, Gerhard; London, Edythe D.

doi:10.1093/ijnp/pyy054

Cited by 14 publications

(8 citation statements)

References 60 publications

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“…At the beginning of the testing session, participants underwent MRI scanning while in the resting state. These procedures were part of a larger testing battery (data reported in Faulkner et al, 2018a and to be reported elsewhere). For smokers, the average duration of abstinence from smoking prior to the resting state fMRI scan was 49.87 minutes (SD = 41.22 minutes).…”

Section: Methodsmentioning

confidence: 99%

Neural Basis of Smoking-Related Difficulties in Emotion Regulation

Faulkner

Dean²,

Ghahremani³

et al. 2020

International Journal of Neuropsychopharmacology

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Background Negative emotional states contribute to cigarette smoking, and difficulties in regulating these states can hinder smoking cessation. Understanding the neural bases of these difficulties in smokers may facilitate development of novel therapies for Tobacco Use Disorder. Methods Thirty-seven participants (18 smokers, 19 nonsmokers; 16–21 years old) completed the Difficulties in Emotion Regulation Scale (DERS), which is comprised of 6 subscales (lack of emotional clarity, lack of emotional awareness, limited access to emotion regulation strategies, nonacceptance of emotional responses, difficulties engaging in goal-directed behaviors, and impulse control difficulties) that combine to provide a total score. Participants also underwent functional magnetic resonance imaging to determine resting-state functional connectivity of the amygdala. Separate ANOVAs were used to determine group differences in self-reports on the DERS. Voxel-wise linear mixed models were performed to determine whether group influenced relationships between whole-brain functional connectivity of the amygdala and scores on the DERS. Results Compared with nonsmokers, smokers reported greater difficulties in emotion regulation, denoted by higher total scores on the DERS. Group differences were observed on a subscale of lack of emotional clarity, but no other subscale differences on the DERS were observed. Nonsmokers exhibited a greater negative correlation than smokers between lack of emotional clarity scores and connectivity of the amygdala with the left inferior frontal gyrus. Finally, this amygdala-to-left inferior frontal gyrus connectivity was weaker in smokers than in nonsmokers. Conclusions These findings suggest that difficulties in emotion regulation in smokers are at least partially due to lack of emotional clarity. Given the role of the inferior frontal gyrus in understanding emotional states, strengthening connectivity between the amygdala and the inferior frontal gyrus may improve emotional clarity to help smokers regulate their negative emotions, thereby improving their ability to quit smoking.

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Section: Methodsmentioning

confidence: 99%

Neural Basis of Smoking-Related Difficulties in Emotion Regulation

Faulkner

Dean²,

Ghahremani³

et al. 2020

International Journal of Neuropsychopharmacology

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“…Exclusion criteria for both studies were self‐report of psychiatric comorbidity; current drug use/abuse or dependence (other than tobacco use disorder or cannabis use); history of neurological injury or disease, pregnancy, and contraindications for MRI (e.g., metal implants). Twenty participants were defined as daily smokers because they smoked at least five cigarettes every day for at least 1 year, in line with definitions in previous research 5,6,8,24–27 ; 24 participants were defined as intermittent smokers because they smoked between one and four cigarettes on at least 1 day per week; 41 participants were defined as nonsmokers because they smoked 0 cigarettes per day. Data from study 1 were collected from November 2015 to March 2018, whereas presented data from study 2 were collected from September 2017 to August 2019.…”

Section: Methodsmentioning

confidence: 96%

Daily and intermittent smoking are associated with low prefrontal volume and low concentrations of prefrontal glutamate, creatine, myo‐inositol, and N‐acetylaspartate

et al. 2020

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Cigarette smoking is still the largest contributor to disease and death worldwide. Successful cessation is hindered by decreases in prefrontal glutamate concentrations and gray matter volume due to daily smoking. Because nondaily, intermittent smoking also contributes greatly to disease and death, understanding whether infrequent tobacco use is associated with reductions in prefrontal glutamate concentrations and gray matter volume may aid public health. Eighty‐five young participants (41 nonsmokers, 24 intermittent smokers, 20 daily smokers, mean age ~23 years old), underwent 1H‐magnetic resonance spectroscopy of the medial prefrontal cortex, as well as structural magnetic resonance imaging (MRI) to determine whole‐brain gray matter volume. Compared with nonsmokers, both daily and intermittent smokers exhibited lower concentrations of glutamate, creatine, N‐acetylaspartate, and myo‐inositol in the medial prefrontal cortex, and lower gray matter volume in the right inferior frontal gyrus; these measures of prefrontal metabolites and structure did not differ between daily and intermittent smokers. Finally, medial prefrontal metabolite concentrations and right inferior frontal gray matter volume were positively correlated, but these relationships were not influenced by smoking status. This study provides the first evidence that both daily and intermittent smoking are associated with low concentrations of glutamate, creatine, N‐acetylaspartate, and myo‐inositol and low gray matter volume in the prefrontal cortex. Future tobacco cessation efforts should not ignore potential deleterious effects of intermittent smoking by considering only daily smokers. Finally, because low glutamate concentrations hinder cessation, treatments that can normalize tonic levels of prefrontal glutamate, such as N‐acetylcysteine, may help intermittent and daily smokers to quit.

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“…Exposure to cigarettes was inferred from the average number of cigarettes smoked per day as in previous research (e.g. Durazzo et al, 2016; Faulkner et al, 2018; 2019; 2020b). Participants also completed the Depression, Anxiety and Stress Scale (DASS), a 42-item questionnaire designed to quantify levels of depression, anxiety and stress; each of these emotional symptoms is assessed by summing the answers to fourteen 4-point Likert scale questions (Lovibond and Lovibond, 1995).…”

Section: Methodsmentioning

confidence: 99%

Relationship Between Depression, Prefrontal Creatine and Gray Matter Volume

Faulkner

Paioni

Kozhuharova

et al. 2021

Preprint

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Background: Depression and low mood are leading contributors to disability worldwide. Research indicates that clinical depression may be associated with low creatine concentrations in the brain and low prefrontal gray matter volume. Because sub-clinical depression also contributes to difficulties in day-to-day life, understanding the neural mechanisms of depressive symptoms in all individuals, even at a sub-clinical level, may aid public health. Methods: Eighty-four young adult participants completed the Depression, Anxiety and Stress Scale (DASS) to quantify severity of depression, anxiety and stress, and underwent 1H-Magnetic Resonance Spectroscopy of the medial prefrontal cortex and structural MRI to determine whole-brain gray matter volume. Results/Outcomes: DASS depression scores were negatively associated with A) concentrations of creatine (but not other metabolites) in the prefrontal cortex, and B) with gray matter volume in the right superior medial frontal gyrus. Medial prefrontal creatine concentrations and right superior medial frontal gray matter volume were positively correlated. DASS anxiety and DASS stress scores were not related to prefrontal metabolite concentrations or whole-brain gray matter volume. Conclusions/Interpretations: This study provides preliminary evidence from a representative group of individuals who exhibit a range of depression levels, that prefrontal creatine and gray matter volume are negatively associated with depression. While future research is needed to fully understand this relationship, these results provide support for previous findings which indicate that increasing creatine concentrations in the prefrontal cortex may improve mood and wellbeing.

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Functional Connectivity of the Raphe Nuclei: Link to Tobacco Withdrawal in Smokers

Cited by 14 publications

References 60 publications

Neural Basis of Smoking-Related Difficulties in Emotion Regulation

Neural Basis of Smoking-Related Difficulties in Emotion Regulation

Daily and intermittent smoking are associated with low prefrontal volume and low concentrations of prefrontal glutamate, creatine, myo‐inositol, and N‐acetylaspartate

Relationship Between Depression, Prefrontal Creatine and Gray Matter Volume

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