BackgroundChildhood adversity is associated with increased risk for mood, anxiety, impulse control, and substance disorders. Although genetic and environmental factors contribute to the development of such disorders, the neurobiological mechanisms involved are poorly understood. A reliable mouse model of early life adversity leading to lasting behavioral changes would facilitate progress in elucidating the molecular mechanisms underlying these adverse effects. Maternal separation is a commonly used model of early life neglect, but has led to inconsistent results in the mouse.ResultsIn an effort to develop a mouse model of early life neglect with long-lasting behavioral effects in C57BL/6 mice, we designed a new maternal separation paradigm that we call Maternal Separation with Early Weaning (MSEW). We tested the effects of MSEW on C57BL/6 mice as well as the genetically distinct DBA/2 strain and found significant MSEW effects on several behavioral tasks (i.e., the open field, elevated plus maze, and forced swim test) when assessed more than two months following the MSEW procedure. Our findings are consistent with MSEW causing effects within multiple behavioral domains in both strains, and suggest increased anxiety, hyperactivity, and behavioral despair in the MSEW offspring. Analysis of pup weights and metabolic parameters showed no evidence for malnutrition in the MSEW pups. Additionally, strain differences in many of the behavioral tests suggest a role for genetic factors in the response to early life neglect.ConclusionsThese results suggest that MSEW may serve as a useful model to examine the complex behavioral abnormalities often apparent in individuals with histories of early life neglect, and may lead to greater understanding of these later life outcomes and offer insight into novel therapeutic strategies.

Background Smoking is the leading cause of preventable death in the US, while abstinence rates remain modest. Smoking has been shown to be perpetuated by operant conditioning, notably negative reinforcement (e.g., smoking to relieve negative affective states). Mindfulness training (MT) shows promise for smoking cessation, by potentially altering an individual’s tendency to smoke in response to craving. The purpose of this study was to examine the effects of MT and mindfulness practice on the relationship between smoking and craving after receiving four weeks of MT. Methods 33 adults received MT as part of a randomized trial for smoking cessation. Individuals in the MT condition recorded formal and informal mindfulness practice during treatment using daily diaries. Results Analyses showed that strong correlations between craving and smoking at baseline (r=0.582) were attenuated at the end of treatment (r=0.126). Mindfulness home practice significantly predicted cigarette use (formal: B=−1.21, p=0.007; informal: B=−1.52, p<0.0001) and informal practice moderated the relationship between craving and smoking at the end of treatment (B=0.52, p=0.03). Conclusions These findings suggest that MT may be effective as a treatment for smoking cessation and that informal mindfulness practice predicts a decoupling of the association between craving and smoking.

Humans suffer heavily from substance use disorders and other addictions. Despite much effort that has been put into understanding the mechanisms of the addictive process, treatment strategies have remained sub-optimal over the past several decades. Mindfulness training, which is based on ancient Buddhist models of human suffering, has recently shown preliminary efficacy in treating addictions. Interestingly, these early models show remarkable similarity to current models of the addictive process, especially in their overlap with operant conditioning (positive and negative reinforcement). Further, they may provide explanatory power for the mechanisms of mindfulness training, including its effects on core addictive elements, such as craving, and the underlying neurobiological processes that may be active therein. In this review, using smoking as an example, we will highlight similarities between ancient and modern views of the addictive process, review studies of mindfulness training for addictions and their effects on craving and other components of this process, and discuss recent neuroimaging findings that may inform our understanding of the neural mechanisms of mindfulness training.

Recent advances in brain imaging have improved the measure of neural processes related to perceptual, cognitive and affective functions, yet the relation between brain activity and subjective experience remains poorly characterized. In part, it is a challenge to obtain reliable accounts of participant’s experience in such studies. Here we addressed this limitation by utilizing experienced meditators who are expert in introspection. We tested a novel method to link objective and subjective data, using real-time fMRI (rt-fMRI) to provide participants with feedback of their own brain activity during an ongoing task. We provided real-time feedback during a focused attention task from the posterior cingulate cortex, a hub of the default mode network shown to be activated during mind-wandering and deactivated during meditation. In a first experiment, both meditators and non-meditators reported significant correspondence between the feedback graph and their subjective experience of focused attention and mind-wandering. When instructed to volitionally decrease the feedback graph, meditators, but not non-meditators, showed significant deactivation of the posterior cingulate cortex. We were able to replicate these results in a separate group of meditators using a novel step-wise rt-fMRI discovery protocol in which participants were not provided with prior knowledge of the expected relationship between their experience and the feedback graph (i.e., focused attention versus mind-wandering). These findings support the feasibility of using rt-fMRI to link objective measures of brain activity with reports of ongoing subjective experience in cognitive neuroscience research, and demonstrate the generalization of expertise in introspective awareness to novel contexts.