Brain Anatomical Alterations in Young Cannabis Users: Is it All Hype? A Meta-Analysis of Structural Neuroimaging Studies.

Introduction: Cannabis use has a high prevalence in young youth and is associated with poor psychosocial outcomes. Such outcomes have been ascribed to the impact of cannabis exposure on the developing brain. However, findings from individual studies of volumetry in youth cannabis users are equivocal. Objectives: Our primary objective was to systematically review the evidence on brain volume differences between young cannabis users and nonusers aged 12-26 where profound neuromaturation occurs, accounting for the role of global brain volumes (GBVs). Our secondary objective was to systematically integrate the findings on the association between youth age and volumetry in youth cannabis users. Finally, we aimed to evaluate the quality of the evidence. Materials and Methods: A systematic search was run in three databases (PubMed, Scopus, and PsycINFO) and was reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We run meta-analyses (with and without controlling for GBV) of brain volume differences between young cannabis users and nonusers. We conducted metaregressions to explore the role of age on volumetric differences. Results: Sixteen studies were included. The reviewed samples included 830 people with mean age 22.5 years (range 14-26 years). Of these, 386 were cannabis users (with cannabis use onset at 15-19 years) and 444 were controls. We found no detectable group differences in any of the GBVs (intracranium, total brain, total white matter, and total gray matter) and regional brain volumes (i.e., hippocampus, amygdala, orbitofrontal cortex, and total cerebellum). Age and cannabis use level did not predict (standardized mean) volume group differences in metaregression. We found little evidence of publication bias (Egger's test p>0.1). Conclusions: Contrary to evidence in adult samples (or in samples mixing adults and youth), previous single studies in young cannabis users, and meta-analyses of brain function in young cannabis users, this early evidence suggests nonsignificant volume differences between young cannabis users and nonusers. While prolonged and long-term exposure to heavy cannabis use may be required to detect gross volume alterations, more studies in young cannabis users are needed to map in detail cannabis-related neuroanatomical changes.

Functional connectivity during feedback learning in smokers.

BACKGROUND: Although it has been traditionally assumed that dysregulation of psychological processes in smokers results from activity within specific brain regions, an emerging view regards such dysregulation as attributable to aberrant communication between distinct brain regions. These processes can be measured during appropriate task paradigms such as the learning from errors task. This study aims to elucidate interactions between brain regions underlying the process of learning from errors, punishment and sensitivity to reward in dependent smokers. METHODS: Functional MRI data from 23 age-matched dependent smokers (8 females, mean age = 25.48, SD = 4.46) and 23 controls (13 females, mean age = 24.83, SD = 5.99) were analysed during a feedback-based associative learning task. Functional connectivity between the dorsal anterior cingulate cortex, nucleus accumbens and reward/sensorimotor areas was investigated during a feedback learning task. RESULTS: Behaviourally, smokers exhibited lower error correction rates and were less sensitive to punishment magnitude. Smokers showed increased functional connectivity between dorsal anterior cingulate cortex/nucleus accumbens seed regions and numerous reward-related target regions including the putamen, anterior cingulate and orbitofrontal cortex. CONCLUSIONS: Reduced learning from errors and widespread aberrant functional connectivity contribute to the emerging functional characterisation of dependent smokers and may bear significant implications when considering the efficacy of smoking interventions.

A systematic review of resting-state functional connectivity in obesity: Refining current neurobiological frameworks and methodological considerations moving forward.

Obesity is the second most common cause of preventable morbidity worldwide. Resting-state functional magnetic resonance imaging (fMRI) has been used extensively to characterise altered communication between brain regions in individuals with obesity, though findings from this research have not yet been systematically evaluated within the context of prominent neurobiological frameworks. This systematic review aggregated resting-state fMRI findings in individuals with obesity and evaluated the contribution of these findings to current neurobiological models. Findings were considered in relation to a triadic model of problematic eating, outlining disrupted communication between reward, inhibitory, and homeostatic systems. We identified a pattern of consistently increased orbitofrontal and decreased insula cortex resting-state functional connectivity in individuals with obesity in comparison to healthy weight controls. BOLD signal amplitude was also increased in people with obesity across studies, predominantly confined to subcortical regions, including the hippocampus, amygdala, and putamen. We posit that altered orbitofrontal cortex connectivity may be indicative of a shift in the valuation of food-based rewards and that dysfunctional insula connectivity likely contributes to altered homeostatic signal processing. Homeostatic violation signals in obesity may be maintained despite satiety, thereby 'hijacking' the executive system and promoting further food intake. Moving forward, we provide a roadmap for more reliable resting-state and task-based functional connectivity experiments, which must be reconciled within a common framework if we are to uncover the interplay between psychological and biological factors within current theoretical frameworks.

Impaired learning from punishment of errors in smokers: Differences in dorsolateral prefrontal cortex and sensorimotor cortex blood-oxygen-level dependent responses.

Cigarette smokers have shown hypersensitivity to reward and hyposensitivity to punishment, along with impairments in learning from errors. The underlying neural mechanism for this failure to adapt performance following an error, particularly when receiving negative feedback, are unclear. Smokers were hypothesized to have poorer error-learning following monetary punishment, associated with hypoactivation in the insula, dorsal anterior cingulate, and hippocampal cortical regions. Twenty-three smokers (8 females, mean age = 25.48, SD = 4.46) and twenty-three healthy controls (13 females, mean age = 24.83, SD = 5.99) were administered an associative learning task, providing monetary reward and punishment for recall performance, during fMRI data collection. Compared with controls, smokers had a lower error-correction rate and were less sensitive to punishment magnitude. Hyperactivity during recall was independent of future error correction, but smokers' successful re-encoding appeared related to higher dorsolateral prefrontal cortex activity while controls had equivalent activation for corrected and repeated errors. While controls showed higher deactivation of the sensorimotor cortex during high punishment, smokers showed higher deactivation during low punishment. The present results support smokers having poorer learning from errors and decreased attentional control associated with hyperactivity in the dorsolateral prefrontal cortex. Additionally, smokers exhibited decreased punishment sensitivity that appeared to limit their ability to adapt learning in the face of repeated negative feedback.

Effects of reward and punishment on learning from errors in smokers.

BACKGROUND: Punishing errors facilitates adaptation in healthy individuals, while aberrant reward and punishment sensitivity in drug-dependent individuals may change this impact. Many societies have institutions that use the concept of punishing drug use behavior, making it important to understand how drug dependency mediates the effects of negative feedback for influencing adaptive behavior. METHODS: Using an associative learning task, we investigated differences in error correction rates of dependent smokers, compared with controls. Two versions of the task were administered to different participant samples: One assessed the effect of varying monetary contingencies to task performance, the other, the presence of reward as compared to avoidance of punishment for correct performance. RESULTS: While smokers recalled associations that were rewarded with a higher value 11% more often than lower rewarded locations, they did not correct higher punished locations more often. Controls exhibited the opposite pattern. The three-way interaction between magnitude, feedback type and group was significant, F(1,48) = 5.288, p =0.026, ɳ2p =0.099. Neither participant group corrected locations offering reward more often than those offering avoidances of punishment. The interaction between group and feedback condition was not significant, F(1,58) = 0.0, p =0.99, ɳ2p =0.001. CONCLUSIONS: The present results suggest that smokers have poorer learning from errors when receiving negative feedback. Moreover, larger rewards reinforce smokers' behavior stronger than smaller rewards, whereas controls made no distinction. These findings support the hypothesis that dependent smokers may respond to positively framed and rewarded anti-smoking programs when compared to those relying on negative feedback or punishment.