1. Short-term meditation induces white matter changes in the anterior cingulate: We previously showed that 3 h of mental training (integrative bodymind training, IBMT), increases ACC activity and improves self-regulation. However, it is not known whether changes in white matter connectivity can result from small amounts of mental training. We here report that 11 h of IBMT increases fractional anisotropy (FA), an index indicating the integrity and efficiency of white matter in the corona radiata, an important white-matter tract connecting the ACC to other structures. We suggest that IBMT could provide a means for improving self-regulation and perhaps reducing or preventing various mental disorders, including smoking dependence. 2. Local and circuit resting-state activity predicts brain activation and behavioral performance during working memory (WM): Resting-state neuronal activity corresponds with task-induced activations. Our goal was to determine if both local and circuit activity in the absence of task performance can predict task activations and whether the rest-task relationship is dependent on task load. Used as an index of local resting-state activity, we found that fractional amplitude of low frequency fluctuations (fALFF) in the middle frontal gyrus and inferior/superior parietal lobule were positively correlated with WM task induced activation, while fALFF in the superior frontal gyrus was negatively correlated with WM task induced deactivation. Resting-state functional connectivity (rsFC) used as an index of circuit activity, showed that the rsFC between frontal and parietal cortices were significantly correlated with WM task activation. The rsFC between task activated and deactivated regions were significantly correlated with both WM task activation and deactivation, while rsFC between task deactivated midline and posterior temporal regions significantly correlated with WM task deactivation. Further, the relationship between the resting-state activity and task-evoked activation in these lateral/superior frontal, inferior/superior parietal, posterior temporal and midline regions was stronger at higher task loads. Additionally, both resting-state activity and task-induced activation in a lateral fronto-parietal circuit were significantly correlated with WM behavioral performance. These findings suggest that intrinsic resting-state activity serves to facilitate brain circuits engaged when performing a cognitive task, and that resting activity can predict task-induced brain responses and behavioral performance. 3. Neural Correlates of Distress Intolerance (DI): This project aims to determine the neurobiological mechanisms that underlie distress tolerance between drug users and controls. Individuals who report high levels of chronic psychosocial stress display greater acute stress-induced activation in corticolimbic regions including the vmPFC, amygdala, insula, and ACC, suggesting that high levels of chronic stress may result in more reactive responses in the face of acute stress, and may require recruitment of more input from prefrontal regulatory regions to cope. Greater distress-induced activation in the bilateral dorsal ACC and the right anterior insula was associated with higher scores on the Barrett Impulsivity Scale (BIS)-Motor subscale, suggesting that impulsive individuals may need more regulatory input from this region to inhibit their actions. The distress phase of the PASAT-M induced greater activation in the insula and ventral ACC relative to the neutral phase of the task. Decreased activation in the prefrontal cortex and parahippocampal gyrus was also observed in the distress phase relative to the neutral. Individuals with low distress tolerance evidenced reduced activation in the subgenual ACC and greater activation in the ventral and dorsal ACC relative to individuals with high DT. Additionally, subjects who reported higher levels of childhood emotional abuse had significantly lower activation in the right vmPFC and the right sACC during a stressful task. Those who reported higher levels of childhood physical abuse had significantly lower activation in the right vmPFC, left vmPFC, and the right sACC, and significantly higher activation in the left OFC. These findings are in line with evidence suggesting that exposure to childhood abuse may lead to hyperactivity of corticotrophin-releasing factor systems that subsequently disrupt development of the cortico-limbic system. 4. Stress induction modulation by a CRHR1 antagonist: We are developing an imaging version of the Trier Social Stress Task to be used first in healthy controls and subsequently in smokers, heavy drinkers and over-eaters. Preliminary results indicate a mild subjective stress response in the absence of stress-induced craving. The task induced robust activation in insula, ACC and right inferior frontal gyrus. We next will be examining if the task increases smoking behavior and then the effects of a pharmacological intervention to reduce the stress/craving response and neuronal activation. 5. Effects of childhood trauma x genotype on brain morphology: In 120 healthy controls, we found that the BDNF Val66Met SNP and early childhood stress interact to alter volume of the superior temporal cortex. The interaction was driven by Met allele carriers with a history of early childhood trauma having smaller volume in this region. There was a negative correlation between total CTQ score and volume for Met allele carriers only, consistent with other reports of Met allele carriers of the BDNF gene being sensitive to early stress. Met allele carriers with high early trauma showed an increase in externally oriented thinking. Resting-state connectivity analyses revealed an interaction between BDNF Val66Met genotype and early childhood trauma between right amygdala and left insula. Additional connectivity analyses are underway using the interaction area found in the volumetric. These data may help our understanding of stress-induced brain plasticity that contributes to drug use vulnerability. 6. Functional polymorphism of the mu-opioid receptor gene (OPRM1) influences reinforcement: Previous reports on the functional effects and phenotypic outcomes of a commonly occurring functional SNP of the mu-opioid receptor (OPRM1 A118G) have been inconsistent. Here we examine its effect on implicit reward learning. We used a probabilistic signal detection task to determine whether this polymorphism impacts response bias to monetary reward in 63 healthy subjects: 51 AA homozygotes and 12 G allele carriers. OPRM1 AA homozygotes exhibited typical responding to the rewarded response (their bias to the rewarded stimulus increased over time). However, OPRM1 G allele carriers exhibited a decline in response compared to the AA homozygotes. These results extend previous reports on the heritability of performance on this task by implicating a specific polymorphism. This may suggest that the polymorphism may confer reduced response to natural reward through a dopamine-mediated decrease during positive reinforcement learning.
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