Ventral Striatum Connectivity During Reward Anticipation in Adolescent Smokers Lee Jollans1, Cao Zhipeng1, Ilknur Icke2, Ciara Greene1, Clare Kelly3, Robert Whelan1, The IMAGEN Consortium 1 Department
of Psychology, University College Dublin, Dublin, Ireland, 2 Bioimaging, School of Medicine, Boston University, Boston, Massachusetts, 3 Discipline of Psychiatry, School of Medicine and Trinity College Institute of Neurosciences, Trinity College Dublin, Dublin, Ireland, Contact:
[email protected]
Introduction Adolescence is a period of substantial behavioral and brain changes. Increased novelty-seeking and choice impulsivity, and reduced harm avoidance are characteristic of adolescence1 and are associated with adolescent smoking2. The heightened propensity for risk-taking in adolescence has been attributed to a relative imbalance between the reward and cognitive control systems in the adolescent brain3. Activation in the ventral striatum (VS), part of the reward system, is associated with adolescent impulsivity4, and is associated with adolescent5 and adult6 smoking frequency.
Method Participants were 206 14-year olds from the IMAGEN study7 with ≥3 lifetime smoking occasions. Functional magnetic resonance imaging was acquired while participants completed the Monetary Incentive Delay (MID) task8. A psychophysiological interaction (PPI) analysis was carried out using the signal time series in two VS regions of interest (ROIs) as the physiological regressor and the effect of task condition (big vs. no win) as the psychological regressor. Functional connectivity between the VS and 92 ROIs based on the Automated Anatomical Labeling atlas9 (& the subthalamic nuclei), as well as substance use and demographic variables were entered into a sophisticated machine learning regression analysis (see Figure 1) to determine which variables were significantly associated with adolescent smoking frequency.
L
Figure 2. ROIs for which functional connectivity with the VS was associated with lifetime smoking. Note. L = Left; R = Right; A = Anterior; P = Posterior; PCC = Posterior Cingulate; IPL = Inferior Parietal Lobule; TP = Temporal Pole; SMG = Supramarginal Gyrus; SOG = Superior Occipital Gyrus; SFG = Superior Frontal Gyrus; MFG = Middle R Frontal Gyrus. Functional connectivity between the VS and nodes drawn in red was positively associated with smoking frequency. Functional connectivity between the VS and nodes drawn in blue was negatively associated with smoking frequency.
Discussion Figure 1. The machine learning analysis was carried out in two stages: (1) The optimal Elastic Net10 parameters for each main cross-validation (CV) fold were identified using nested CV, using bootstrap aggregation. (2) The optimal Elastic Net parameters were applied to the full training set (90% of the data) in each main CV fold. The resulting beta weights were used to generate outcome predictions for the remaining 10% of the dataset. Goodness-of-fit was estimated using the outcome predictions across test sets from all main CV folds.
Results There was a significant association between lifetime smoking and both right (mean r = .27) and left (mean r = .21) VS functional connectivity. See Figure 2 for ROIs that significantly contributed to the regression models.
The PPI analysis produced two key findings with respect to adolescent smoking frequency and functional connectivity with the VS during anticipation of rewards: (1) a positive association within the reward system; specifically, between the VS and OFC and amygdala, (2) a negative correlation between the reward system and inhibitory control and attention networks; specifically, between VS and the right IFG, inferior parietal cortex, and medial prefrontal cortex. The increased functional connectivity between the VS and OFC and PPC with increased smoking suggests that adolescent smoking may be associated with increased attribution of salience to reward-related stimuli. Furthermore, the finding of reduced functional connectivity between the VS and the right IFG, mPFC, and inferior parietal cortex with increased smoking indicates a deficit in inhibitory control and attentional orienting. Taken together, these findings paint a picture of increased valuation of rewards, alongside difficulties inhibiting behavior, and possibly a deficit in the integration of sensory and motivational cues in adolescent smokers.
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