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Rationale: Women with cocaine use disorder have worse treatment outcomes compared with men. Sex differences in cocaine addiction may be driven by differences in neurobiology or stress reactivity. Oxytocin is a potential therapeutic for stress reduction in substance use disorders, but no studies have examined the effect of oxytocin on neural response to drug cues in individuals with cocaine use disorders or potential sex differences in this response. Objectives: The goal of this study was to examine the effect of intranasal oxytocin on cocaine cue reactivity in cocaine dependence, modulated by gender and history of childhood trauma. Methods: Cocaine-dependent men with (n = 24) or without (n = 19) a history of childhood trauma and cocaine-dependent women with (n = 16) or without (n = 8) a history of childhood trauma completed an fMRI cocaine cue reactivity task under intranasal placebo or oxytocin (40 IU) on two different days. fMRI response was measured in the right amygdala and dorsomedial prefrontal cortex (DMPFC). Results: In the DMPFC, oxytocin reduced fMRI response to cocaine cues across all subject groups. However, in the amygdala, only men with a history of childhood trauma showed a significantly reduced fMRI response to cocaine cues on oxytocin versus placebo, while women with a history of childhood trauma showed an enhanced amygdala response to cocaine cues following oxytocin administration. Cocaine-dependent subjects with no history of childhood trauma showed no effect of oxytocin on amygdala response. Conclusions: Oxytocin can reduce cue reactivity in cocaine dependence, but its effect is modified by sex and childhood trauma history. Whereas men with cocaine dependence may benefit from oxytocin administration, additional studies are needed to determine whether oxytocin can be an effective therapeutic for cocaine-dependent women. [ABSTRACT FROM AUTHOR]

Combining pharmacological interventions with evidence-based behavioral interventions may help optimize treatment outcomes for alcohol use disorder (AUD). While several effective behavioral interventions for AUD have been developed, the vast majority target individual patients, despite evidence that behavioral interventions for couples have the ability to outperform individual treatments for AUD. Alcohol Behavioral Couples Therapy (ABCT) is an evidence-based behavioral intervention for couples that has been shown to significantly reduce AUD severity as well as improve relationship functioning. Accumulating evidence suggests that the neuropeptide oxytocin has the ability to reduce alcohol craving and consumption, symptoms of tolerance and withdrawal, and ameliorate neurobiological deficits associated with AUD. Furthermore, oxytocin has demonstrated the ability to increase prosocial behavior and cognition, and restore sensitivity to natural rewards such as interpersonal relationships. No study to date has examined the ability of oxytocin to enhance ABCT. Thus, the primary objective of this Phase II study is to examine the effects of oxytocin versus placebo in combination with ABCT in reducing AUD severity and improving relationship functioning. We also will utilize neuroimaging techniques before and after treatment to investigate the underlying pathophysiology of AUD among couples and identify prognostic indicators of treatment outcome. The findings from this study might provide critical new information to help inform clinical practice and accelerate research on the pharmacological treatment of AUD. [ABSTRACT FROM AUTHOR]

The monetary incentive delay (MID) task is a widely used probe for isolating neural circuitry in the human brain associated with incentive motivation. In the present functional magnetic resonance imaging (fMRI) study, 82 young adults, characterized along dimensions of impulsive sensation seeking, completed a MID task. fMRI and behavioral incentive functions were decomposed into incentive valence and magnitude parameters, which were used as predictors in linear regression to determine whether mesolimbic response is associated with problem drinking and recent alcohol use. Alcohol use was best explained by higher fMRI response to anticipation of losses and feedback on high gains in the thalamus. In contrast, problem drinking was best explained by reduced sensitivity to large incentive values in mesolimbic regions in the anticipation phase and increased sensitivity to small incentive values in the dorsal caudate nucleus in the feedback phase. Altered fMRI responses to monetary incentives in mesolimbic circuitry, particularly those alterations associated with problem drinking, may serve as potential early indicators of substance abuse trajectories. [ABSTRACT FROM AUTHOR]

Abstract: Working memory is a cognitive function that is affected by aging and disease. To better understand the neural substrates for working memory, the present study examined the influence of estradiol on working memory using functional magnetic resonance imaging. Pre-menopausal women were tested on a verbal n-back task during the early (EF) and late follicular (LF) phases of the menstrual cycle. Although brain activation patterns were similar across the two phases, the most striking pattern that emerged was that estradiol had different associations with the two hemispheres. Increased activation in left frontal circuitry in the LF phase was associated with increased estradiol levels and decrements in working memory performance. In contrast, increased activation in right hemisphere regions in the LF phase was associated with improved task performance. The present study showed that better performance in the LF than the EF phase was associated with a pattern of reduced recruitment of the left-hemisphere and increased recruitment of the right-hemisphere in the LF compared to EF phase. We speculate that estradiol interferes with left-hemisphere working-memory processing in the LF phase, but that recruitment of the right hemisphere can compensate for left-hemisphere interference. This may be related to the proposal that estradiol can reduce cerebral asymmetries by modulating transcallosal communication (Hausmann, 2005). [Copyright &y& Elsevier]

Introduction Face processing undergoes significant developmental change with age. Two kinds of developmental changes in face specialization were examined in this study: specialized maturation, or the continued tuning of a region to faces but little change in the tuning to other categories; and competitive interactions, or the continued tuning to faces accompanied by decreased tuning to nonfaces (i.e., pruning). Methods Using fMRI, in regions where adults showed a face preference, a face- and object-specialization index were computed for younger children (5-8 years), older children (9-12 years) and adults (18-45 years). The specialization index was scaled to each subject's maximum activation magnitude in each region to control for overall age differences in the activation level. Results Although no regions showed significant face specialization in the younger age group, regions strongly associated with social cognition (e.g., right posterior superior temporal sulcus, right inferior orbital cortex) showed specialized maturation, in which tuning to faces increased with age but there was no pruning of nonface responses. Conversely, regions that are associated with more basic perceptual processing or motor mirroring (right middle temporal cortex, right inferior occipital cortex, right inferior frontal opercular cortex) showed competitive interactions in which tuning to faces was accompanied by pruning of object responses with age. Conclusions The overall findings suggest that cortical maturation for face processing is regional-specific and involves both increased tuning to faces and diminished response to nonfaces. Regions that show competitive interactions likely support a more generalized function that is co-opted for face processing with development, whereas regions that show specialized maturation increase their tuning to faces, potentially in an activity-dependent, experience-driven manner. [ABSTRACT FROM AUTHOR]

We manipulated the degree of structural similarity between objects that had to be matched either according to whether they represented the same object (perceptual matching) or belonged to the same category (conceptual matching). Behaviorally, performance improved as a linear function of increased structural similarity during conceptual matching but deteriorated as a linear function of increased structural similarity during perceptual matching. These effects were mirrored in fMRI recordings where activation in several ventral posterior areas exhibited a similar interaction between match type and structural similarity. Our findings provide direct support for the notion that structural similarity exerts opposing effects on classification depending on whether objects are to be perceptually differentiated or categorized--a notion that has been based on rather circumstantial evidence. In particular, the finding that structural similarity plays a major role in categorization of instances according to taxonomy challenges the view that the organization of superordinate categories is not driven by shared structural features. [ABSTRACT FROM AUTHOR]

The misfortunes of enviable individuals are met by observers with pleasure whereas those of “average”, non-enviable individuals elicit pain. These responses are mirrored in deservingness judgments, as enviable individuals’ misfortunes are perceived as deserved and those of non-enviable individuals perceived as undeserved. However, the neural underpinnings of these deservingness disparities remain unknown. To explore this phenomenon, we utilized fMRI to test the hypotheses that (A) non-enviable targets’ misfortunes would be associated with activation of brain regions that mediate empathic responding (pain matrix, mentalizing network) and not for enviable targets and (B) that activation of those regions would predict decreases in deservingness judgments. Supporting our first hypothesis, the misfortunes of non-enviable targets (as opposed to good fortunes) were associated with activation of the mentalizing network: medial prefrontal cortex, posterior cingulate cortex, temporal–parietal junction, and anterior temporal lobes. Supporting our second hypothesis, dorsomedial prefrontal cortex activation from this contrast was negatively correlated with subsequent reports of how much the non-enviable target deserved his/her misfortune. These findings suggest that non-enviable individuals’ misfortunes are perceived as unjust due, in part, to the recruitment of the mentalizing network. [ABSTRACT FROM AUTHOR]

Abstract: High sensation seeking is associated with strong approach behaviors and weak avoidance responses. The present study used functional magnetic resonance imaging (fMRI) to further characterize the neurobiological underpinnings of this behavioral profile using a Go/No-go task. Analysis of brain activation associated with response inhibition (No-go) versus response initiation and execution (Go) revealed the commonly reported right lateral prefrontal, insula, cingulate, and supplementary motor area network. However, right lateral activation was associated with greater No-go than Go responses only in low sensation seekers. High sensation seekers showed no differential activation in these regions but a more pronounced Go compared to No-go response in several other regions that are involved in salience detection (insula), motor initiation (anterior cingulate) and attention (inferior parietal cortex). Temporal analysis of the hemodynamic response for Go and No-go conditions revealed that the stronger response to Go than No-go trials in high sensation seekers occurred in in the earliest time window in the right middle frontal gyrus, right mid-cingulate and right precuneus. In contrast, the greater No-go than Go response in low sensation seekers occurred in the later time window in these same regions. These findings indicate that high sensation seekers more strongly attend to or process Go trials and show delayed or minimal inhibitory responses on No-go trials in regions that low sensation seekers use for response inhibition. Failure to engage such regions for response inhibition may underlie some of the risky and impulsive behaviors observed in high sensation seekers. [Copyright &y& Elsevier]

Alcohol use disorder (AUD) and posttraumatic stress disorder (PTSD) are two prevalent psychiatric conditions in the U.S. The co-occurrence of AUD and PTSD is also common, and associated with a more severe clinical presentation and worse treatment outcomes across the biopsychosocial spectrum (e.g., social and vocational functioning, physical health) as compared to either disorder alone. Despite the high co-occurrence and negative outcomes, research on effective medications for AUD/PTSD is sparse and there is little empirical evidence to guide treatment decisions. The study described in this paper addresses this knowledge gap by testing the efficacy of N -acetylcysteine (NAC) in reducing alcohol use and PTSD symptoms. Animal studies and prior clinical research suggest a role for NAC in the treatment of substance use disorders and PTSD via glutamate modulation. NAC is a cysteine pro-drug that stimulates the cystine-glutamate exchanger, normalizes glial glutamate transporters, and restores glutamatergic tone on presynaptic receptors in reward regions of the brain. Moreover, NAC is available over-the-counter, has a long-established safety record, and does not require titration to achieve the target dose. This paper describes the rationale, study design, and methodology of a 12-week, randomized, double-blind, placebo-controlled trial of NAC (2400 mg/day) among adults with co-occurring AUD and PTSD. Functional magnetic resonance imaging (fMRI) and proton magnetic resonance spectroscopy (1H-MRS) are utilized to investigate the neural circuitry and neurochemistry underlying comorbid AUD/PTSD and identify predictors of treatment outcome. This study is designed to determine the efficacy of NAC in the treatment of co-occurring AUD/PTSD and provide new information regarding mechanisms of action implicated in co-occurring AUD/PTSD. • Alcohol use disorder (AUD) and posttraumatic stress disorder (PTSD) frequently co-occur. • Medications that normalize glutamatergic dysregulation, such as NAC, are potential pharmacotherapies for AUD/PTSD treatment. • This paper describes the rationale, study design and methods of a randomized controlled trial of NAC for AUD/PTSD treatment. • FMRI and 1H-MRS are utilized to elucidate behavioral and neurobiological mechanisms underlying comorbid AUD/PTSD. [ABSTRACT FROM AUTHOR]