Substance use, anxiety, and self-management efficacy in HIV-positive individuals: A mediation analysis.

CONTEXT: In China, the social stigma of both substance use and HIV remains major barriers. HIV+ individuals have been demonstrated to have higher psychosocial distress in the literature. To ensure quality of life among HIV+ Chinese individuals, self-efficacy in HIV-related management including substance use and anxiety is the key to suppress viral load and maintain healthy lives. OBJECTIVES: We examine the mediation relationship among substance use, anxiety, and self-management efficacy. METHOD: A cross-sectional study design was used. 137 HIV+ individuals were recruited from two premier Chinese hospitals: Beijing's Ditan Hospital and Shanghai's Public Health Clinic Center (SPHCC). RESULTS: HIV+ substance users had significantly lower HIV-management efficacy and higher anxiety scores. About a third of the relations between substance use and anxiety was mediated by HIV-management self-efficacy. Those who used substances in the previous week had higher anxiety levels suggesting the presence of a recent effect. Their higher levels of anxiety could be largely explained by their lower HIV-management efficacy. CONCLUSION: It is useful for healthcare providers to assess substance use behaviors in HIV+ individuals as well as provide support in managing anxiety in this population. Meanwhile, enhancing self-management efficacy to ensure healthy lifestyles may support achieving optimal lives with HIV.

Clinical characteristics and diagnostic confirmation of Internet addiction in secondary school students in Wuhan, China.

AIM: This study investigated the clinical characteristics of internet addiction using a cross-sectional survey and psychiatric interview. METHODS: A structured questionnaire consisted of demographics, Symptom Checklist 90, Self-Rating Anxiety Scale, Self-Rating Depression Scale, and Young's Internet Addiction Test (YIAT) was administered to students of two secondary schools in Wuhan, China. Students with a score of 5 or higher on the YIAT were classified as having Internet Addiction Disorder (IAD). Two psychiatrists interviewed students with IAD to confirm the diagnosis and evaluate their clinical characteristics. RESULTS: Of a total of 1076 respondents (mean age 15.4 ± 1.7 years; 54.1% boys), 12.6% (n = 136) met the YIAT criteria for IAD. Clinical interviews ascertained the Internet addiction of 136 pupils and also identified 20 students (14.7% of IAD group) with comorbid psychiatric disorders. Results from multinomial logistic regression indicated that being male, in grade 7-9, poor relationship between parents and higher self-reported depression scores were significantly associated with the diagnosis of IAD. CONCLUSION: These results advance our understanding of the clinical characteristics of Internet addiction in Chinese secondary school students and may help clinicians, teachers, and other stakeholders better manage this increasingly serious mental condition.

Functional Networks of Reward and Punishment Processing and Their Molecular Profiles Predicting the Severity of Young Adult Drinking.

Alcohol misuse is associated with altered punishment and reward processing. Here, we investigated neural network responses to reward and punishment and the molecular profiles of the connectivity features predicting alcohol use severity in young adults. We curated the Human Connectome Project data and employed connectome-based predictive modeling (CPM) to examine how functional connectivity (FC) features during wins and losses are associated with alcohol use severity, quantified by Semi-Structured Assessment for the Genetics of Alcoholism, in 981 young adults. We combined the CPM findings and the JuSpace toolbox to characterize the molecular profiles of the network connectivity features of alcohol use severity. The connectomics predicting alcohol use severity appeared specific, comprising less than 0.12% of all features, including medial frontal, motor/sensory, and cerebellum/brainstem networks during punishment processing and medial frontal, fronto-parietal, and motor/sensory networks during reward processing. Spatial correlation analyses showed that these networks were associated predominantly with serotonergic and GABAa signaling. To conclude, a distinct pattern of network connectivity predicted alcohol use severity in young adult drinkers. These "neural fingerprints" elucidate how alcohol misuse impacts the brain and provide evidence of new targets for future intervention.

Clinical and behavior characteristics of individuals who used ketamine.

This study aims to depict and compare clinical characteristics and risk behavior among groups of individuals using ketamine, polydrugs or smoking cigarette. A total of 185 drug-using participants and 49 smokers participated in this study. A cross-sectional interview was used to collect information on demographics, drug- and sex-related behaviors, HIV serostatus, lower urinary tract symptoms (LUTS), behavioral dispositions. N-back memory test was used to measure short-term memory. Result shows that 10 participants (5.41%) were HIV positive and 14 (7.57%) having LUTS. Individuals with ketamine and polydrugs use have significantly worse drug-related problem than cigarette smokers. Compared to cigarette smokers and ketamine users, individuals with polydrug users scored significantly higher on impulsivity measures. Cigarette smokers performed significantly better than the other two groups on the memory tests. A few patients had been infected with HIV and diagnosed with LUTS. Findings support that memory on short term recalls of patients with ketamine use might be impaired. Study findings warrants the necessarily of further study on influences of using ketamine.

Traumatic Experiences and PTSD Symptoms in the Chinese Male Intrafamilial Physical Violence Perpetrators: A Comparative and Structural Equation Modeling Study.

We aimed to compare traumatic experiences among the groups of perpetrators with or without violent pedigree, and establish a structural model of posttraumatic stress disorder (PTSD) symptoms as mediators of traumatic experiences and severe intrafamilial physical violence among Chinese male perpetrators. A cross-sectional survey and a face-to-face interview were conducted to examine intimate partner violence (IPV) perpetration and violent pedigree, childhood maltreatment, other traumatic events, PTSD symptoms, and severe intrafamilial physical violence in a community sample of 229 abusive men and 303 controlled men in China. Using structural equation modeling (SEM) techniques, the scores of the questionnaires were entered into the theoretical model and calculated. Findings demonstrated that the numbers of the traumatic events in four groups were significantly different with a declining trend, and the SEM data had an adequate fit. The loadings of pathways from childhood witness domestic violence (DV) to severe physical violence (SPV) were more salience than other pathways, and the indirect effect of every pathway, except for the childhood witness DV to PTSD symptoms, on severe intrafamilial physical violence in the model was significant. The results suggest that PTSD symptoms cluster as mediator of the intergenerational transmission of SPV perpetration in Chinese abusive men. Childhood witness IPV has effects on adulthood perpetration of IPV.

Sex differences in the neuroanatomy of alcohol dependence: hippocampus and amygdala subregions in a sample of 966 people from the ENIGMA Addiction Working Group.

Males and females with alcohol dependence have distinct mental health and cognitive problems. Animal models of addiction postulate that the underlying neurobiological mechanisms are partially distinct, but there is little evidence of sex differences in humans with alcohol dependence as most neuroimaging studies have been conducted in males. We examined hippocampal and amygdala subregions in a large sample of 966 people from the ENIGMA Addiction Working Group. This comprised 643 people with alcohol dependence (225 females), and a comparison group of 323 people without alcohol dependence (98 females). Males with alcohol dependence had smaller volumes of the total amygdala and its basolateral nucleus than male controls, that exacerbated with alcohol dose. Alcohol dependence was also associated with smaller volumes of the hippocampus and its CA1 and subiculum subfield volumes in both males and females. In summary, hippocampal and amygdalar subregions may be sensitive to both shared and distinct mechanisms in alcohol-dependent males and females.

Functional connectivity delineates distinct roles of the inferior frontal cortex and presupplementary motor area in stop signal inhibition.

The neural basis of motor response inhibition has drawn considerable attention in recent imaging literature. Many studies have used the go/no-go or stop signal task to examine the neural processes underlying motor response inhibition. In particular, showing greater activity during no-go (stop) compared with go trials and during stop success compared with stop error trials, the right inferior prefrontal cortex (IFC) has been suggested by numerous studies as the cortical area mediating response inhibition. Many of these same studies as well as others have also implicated the presupplementary motor area (preSMA) in this process, in accord with a function of the medial prefrontal cortex in goal-directed action. Here we used connectivity analyses to delineate the roles of IFC and preSMA during stop signal inhibition. Specifically, we hypothesized that, as an integral part of the ventral attention system, the IFC responds to a stop signal and expedites the stop process in the preSMA, the primary site of motor response inhibition. This hypothesis predicted that preSMA and primary motor cortex would show functional interconnectivity via the basal ganglia circuitry to mediate response execution or inhibition, whereas the IFC would influence the basal ganglia circuitry via connectivity with preSMA. The results of Granger causality analyses in 57 participants confirmed this hypothesis. Furthermore, psychophysiological interaction showed that, compared with stop errors, stop successes evoked greater effective connectivity between the IFC and preSMA, providing additional support for this hypothesis. These new findings provided evidence critically differentiating the roles of IFC and preSMA during stop signal inhibition and have important implications for our understanding of the component processes of inhibitory control.

A neural measure of behavioral engagement: task-residual low-frequency blood oxygenation level-dependent activity in the precuneus.

Brain imaging has provided a useful tool to examine the neural processes underlying human cognition. A critical question is whether and how task engagement influences the observed regional brain activations. Here we highlighted this issue and derived a neural measure of task engagement from the task-residual low-frequency blood oxygenation level-dependent (BOLD) activity in the precuneus. Using independent component analysis, we identified brain regions in the default circuit - including the precuneus and medial prefrontal cortex (mPFC) - showing greater activation during resting as compared to task residuals in 33 individuals. Time series correlations with the posterior cingulate cortex as the seed region showed that connectivity with the precuneus was significantly stronger during resting as compared to task residuals. We hypothesized that if the task-residual BOLD activity in the precuneus reflects engagement, it should account for a certain amount of variance in task-related regional brain activation. In an additional experiment of 59 individuals performing a stop signal task, we observed that the fractional amplitude of low-frequency fluctuation (fALFF) of the precuneus but not the mPFC accounted for approximately 10% of the variance in prefrontal activation related to attentional monitoring and response inhibition. Taken together, these results suggest that task-residual fALFF in the precuneus may be a potential indicator of task engagement. This measurement may serve as a useful covariate in identifying motivation-independent neural processes that underlie the pathogenesis of a psychiatric or neurological condition.

Neural correlates of speeded as compared with delayed responses in a stop signal task: an indirect analog of risk taking and association with an anxiety trait.

The stop signal task (SST) is widely used to explore neural processes involved in cognitive control. By randomly intermixing stop and go trials and imposing on participants to respond quickly to the go but not the stop signal, the SST also introduces an indirect element of risk, which participants may avert by slowing down or ignore by responding "as usual," during go trials. This "risk-taking" component of the SST has to our knowledge never been investigated. The current study took advantage of variability of go trial reaction time (RT) and compared the post-go go trials that showed a decrease in RT (risk-taking decision) and those post-go go trials that showed an increase in RT ("risk-aversive" decision) in 33 healthy individuals who underwent functional magnetic resonance imaging during the SST. This contrast revealed robust activation in bilateral visual cortices as well as left inferior parietal and posterior cingulate cortices, amygdala, and middle frontal gyrus (P < 0.05, family-wise error [FWE] corrected). Furthermore, we observed that the magnitude of amygdala activity is positively correlated with trait anxiety of the participants. These results thus delineated, for the first time, a neural analog of risk taking during stop signal performance, highlighting a novel aspect and broadening the utility of this behavioral paradigm.

Altered impulse control in alcohol dependence: neural measures of stop signal performance.

BACKGROUND: Altered impulse control has been implicated in the shaping of habitual alcohol use and eventual alcohol dependence. We sought to identify the neural correlates of altered impulse control in 24 abstinent patients with alcohol dependence (PAD), as compared to 24 demographics matched healthy control subjects (HC). In particular, we examined the processes of risk taking and cognitive control as the neural endophenotypes of alcohol dependence. METHODS: To this end, functional magnetic resonance imaging (fMRI) was conducted during a stop signal task (SST), in which a procedure was used to elicit errors in the participants. The paradigm allowed trial-by-trial evaluation of response inhibition, error processing, and post-error behavioral adjustment. Furthermore, by imposing on the subjects to be both fast and accurate, the SST also introduced a distinct element of risk, which participants may or may not avert during the task. Brain imaging data were analyzed with Statistical Parametric Mapping in covariance analyses accounting for group disparity in general performance. RESULTS: The results showed that, compared to HC, PAD demonstrated longer go trial reaction time (RT) and higher stop success rate (SS%). HC and PAD were indistinguishable in stop signal reaction time (SSRT) and post-error slowing (PES). In a covariance analysis accounting for go trial RT and SS%, HC showed greater activity in the left dorsolateral prefrontal cortex than PAD, when subjects with short and long SSRT were contrasted. By comparing PAD and HC directly during stop errors (SE), as contrasted with SS, we observed greater activity in PAD in bilateral visual and frontal cortices. Compared to HC, PAD showed less activation of the right dorsolateral prefrontal cortex during PES, an index of post-error behavioral adjustment. Furthermore, PAD who showed higher alcohol urge at the time of the fMRI were particularly impaired in dorsolateral prefrontal activation, as compared to those with lower alcohol urge. Finally, compared to HC subjects, PAD showed less activity in cortical and subcortical structures including putamen, insula, and amygdala during risk-taking decisions in the SST. CONCLUSION: These preliminary results provided evidence for altered neural processing during impulse control in PAD. These findings may provide a useful neural signature in the evaluation of treatment outcomes and development of novel pharmacotherapy for alcohol dependence.

Decreased amygdala activation during risk taking in non-dependent habitual alcohol users: A preliminary fMRI study of the stop signal task.

BACKGROUND AND OBJECTIVES: Habitual alcohol use is prodromal to alcohol dependence. It has been suggested that impairment in impulse control contributes to habitual drinking. Little is known whether neural processes associated with impulse control is altered in non-dependent social drinkers. The current preliminary study combined functional magnetic resonance imaging and the stop signal task (SST) to address this issue. METHODS: We compared non-dependent non/light (n = 12) and moderate/heavy (n = 9) young adult alcohol drinkers in a SST, in which they were required to exercise inhibitory control during the stop trials and were engaged in a speed/accuracy trade-off during trial-to-trial go responses. Our previous studies identified neural correlates of inhibitory control and risk taking during the SST ( [10] , [11] ). Furthermore, alcohol dependent patients showed altered brain activation both during inhibitory control and risk taking, compared to healthy controls ( [12] ). RESULTS: We showed that moderate/heavy alcohol drinkers were decreased in amygdala activation during risk taking, while indistinguishable in neural measures of inhibitory control, when compared to non/light drinkers. CONCLUSIONS AND SIGNIFICANCE: Altered amygdala activation during risk taking may be a key neural process underlying early habitual alcohol use and a potential marker mediating transition to alcohol dependence.

Neuronal correlates of kinematics-to-dynamics transformation in the supplementary motor area.

It is widely acknowledged that movements are planned at the level of the kinematics. However, the central nervous system must ultimately transform kinematic plans into dynamics-related commands. How, when, and where the kinematics-to-dynamics (KD) transformation is processed represent fundamental and unanswered questions. We recorded from the supplementary motor area (SMA) of two monkeys as they executed visually instructed reaching movements. We specifically analyzed a delay period following the instruction but prior to the go signal (motor planning). During the delay, a group of neurons in the SMA progressively came to reflect the dynamics rather than the desired kinematics of the upcoming movement. This finding suggests that some neurons in the SMA participate in the KD transformation.

Inhibitory control and emotional stress regulation: neuroimaging evidence for frontal-limbic dysfunction in psycho-stimulant addiction.

This review focuses on neuroimaging studies that examined stress processing and regulation and cognitive inhibitory control in patients with psycho-stimulant addiction. We provide an overview of these studies, summarizing converging evidence and discrepancies as they occur in the literature. We also adopt an analytic perspective and dissect these psychological processes into their sub-components, to identify the neural pathways specific to each component process and those that are more specifically involved in psycho-stimulant addiction. To this aim we refer frequently to studies conducted in healthy individuals. Despite the separate treatment of stress/affect regulation, stress-related craving or compulsive drug seeking, and inhibitory control, neural underpinnings of these processes overlap significantly. In particular, the ventromedial prefrontal regions including the anterior cingulate cortex, amygdala and the striatum are implicated in psychostimulant dependence. Our overarching thesis is that prefrontal activity ensures intact emotional stress regulation and inhibitory control. Altered prefrontal activity along with heightened striatal responses to addicted drug and drug-related salient stimuli perpetuates habitual drug seeking. Further studies that examine the functional relationships of these neural systems will likely provide the key to understanding the mechanisms underlying compulsive drug use behaviors in psycho-stimulant dependence.

Neural correlates of impulse control during stop signal inhibition in cocaine-dependent men.

Altered impulse control is associated with substance use disorders, including cocaine dependence. We sought to identify the neural correlates of impulse control in abstinent male patients with cocaine dependence (PCD). Functional magnetic resonance imaging (fMRI) was conducted during a stop signal task that allowed trial-by-trial evaluation of response inhibition. Fifteen male PCD and 15 healthy control (HC) subjects, matched in age and years of education, were compared. Stop signal reaction time (SSRT) was derived on the basis of a horse race model. By comparing PCD and HC co-varied for stop success rate, task-related frustration rating, and post-error slowing, we isolated the neural substrates of response inhibition, independent of attentional monitoring (of the stop signal) and post-response processes including affective responses and error monitoring. Using region of interest analysis, we found no differences between HC and PCD who were matched in stop signal performance in the pre-supplementary motor area (pre-SMA) previously shown to be associated with SSRT. However, compared with HC, PCD demonstrated less activation of the rostral anterior cingulate cortex (rACC), an area thought to be involved in the control of stop signal inhibition. The magnitude of rACC activation also correlated negatively with the total score and the impulse control subscore of the Difficulty in Emotion Regulation Scale in PCD. The current study thus identified the neural correlates of altered impulse control in PCD independent of other cognitive processes that may influence stop signal performance. Relative hypoactivation of the rACC during response inhibition may represent a useful neural marker of difficulties in impulse control in abstinent cocaine-dependent men who are at risk of relapse.

Imaging response inhibition in a stop-signal task: neural correlates independent of signal monitoring and post-response processing.

Execution of higher cortical functions requires inhibitory control to restrain habitual responses and meet changing task demands. We used functional magnetic resonance imaging to show the neural correlates of response inhibition during a stop-signal task. The task has a frequent "go" stimulus to set up a pre-potent response tendency and a less frequent "stop" signal for subjects to withhold their response. We contrasted brain activation between successful and failed inhibition for individual subjects and compared groups of subjects with short and long stop-signal reaction times. The two groups of subjects did not differ in their inhibition failure rates or the extent of signal monitoring, error monitoring, or task-associated frustration ratings. The results showed that short stop-signal reaction time or more efficient response inhibition was associated with greater activation in the superior medial and precentral frontal cortices. Moreover, activation of these inhibitory motor areas correlated negatively with stop-signal reaction time. These brain regions may represent the neural substrata of response inhibition independent of other cognitive and affective functions.

Obsessive-compulsiveness and impulsivity in a non-clinical population of adolescent males and females.

Obsessive-compulsive and impulsive behaviors co-occur in certain psychiatric conditions. Some have suggested that these disturbances constitute a spectrum of altered psychologies and behaviors that share an underlying neuropathology. We investigate here whether obsessive-compulsiveness and impulsivity reflect related psychological dimensions in a non-clinical adolescent population. Out of 720 high-school students, 672 and 682 completed a questionnaire interview with a Chinese version of the Maudsley Obsessive-Compulsive Inventory (MOCI) and the Barratt Impulsiveness Scale (BIS-11), respectively. Both MOCI and BIS-11 demonstrated good overall internal consistency, each with three major factors identified with Principal Component Analysis. In the 638 participants who completed both questionnaires, the total MOCI and BIS-11 scores did not correlate with each other. However, the MOCI factor "repetitive checking and attention to details" correlated negatively with the BIS-11 factor "inability to plan and look ahead" for all participants, and for males and females separately. The same MOCI factor also correlated negatively with the BIS-11 factors "lack of perseverance and self-control" and "novelty-seeking and acting without thinking" for all participants, and for females but not for males. The MOCI factor "doubt and intrusive thoughts" correlated positively with the BIS-11 factor "lack of perseverance and self-control" for all participants, and for males but not for females. These results suggested that the relationship between obsessive-compulsiveness and impulsivity as measured by the MOCI and the BIS-11 is complicated, with gender playing an important modulatory role. We discuss the relevance of these findings to developing a conceptual scheme to characterize and study the neurobiological basis of obsessive-compulsive and impulsive behaviors.

Performance monitoring and stop signal inhibition in abstinent patients with cocaine dependence.

Impulsivity has been associated with drug abuse and relapse. As a measure of impulsivity, response inhibition in a stop signal task is impaired in substance abusers compared to healthy control subjects. However, cognitive processes besides response inhibition can affect performance in the stop signal task. Greater response readiness to the go signal increases stop signal reaction time (SSRT) and greater performance monitoring elicited by the stop signal decreases SSRT. Prolonged SSRT, therefore, may reflect differences in these other task-related cognitive processes rather than impaired response inhibition. Using a tracking stop-signal task, we compared 18 abstinent cocaine dependent patients with 41 age- and education-matched healthy controls. We computed SSRT for each individual subject on the basis of the horse race model. We also computed the fore-period (FP) effect to measure response readiness to the go signal and the post-signal slowing (PSS) effect to measure performance monitoring to the stop signal. Cocaine subjects showed increased SSRT and decreased PSS effect, compared to healthy controls. Covariance adjustment for the PSS effect eliminated the SSRT difference from healthy controls. These results suggest that diminished performance monitoring can be a critical cognitive mechanism underlying impaired response inhibition in cocaine dependent patients.

Sex differences in brain activation during stress imagery in abstinent cocaine users: a functional magnetic resonance imaging study.

BACKGROUND: Because stress mediates drug seeking and relapse, and sex differences have been observed in stress and in the development of cocaine addiction, in this study we used functional neuroimaging to examine the effect of sex on stress responses in abstinent cocaine users. METHODS: In a functional magnetic resonance imaging session, 17 male and 10 female cocaine-dependent subjects participated in script-guided imagery of neutral or stress situations. Subjects rated imagery vividness, anxiety, and cocaine craving for each trial. Brain activation during the stress and neutral imagery periods relative to their own baseline was examined in individual subjects. Sex contrast was obtained in second-level group analysis. RESULTS: Female subjects demonstrated more activation, compared with male subjects, in left middle frontal, anterior cingulate, and inferior frontal cortices and insula, and right cingulate cortex during stress imagery. Region of interest analysis showed that the change of activity in left anterior cingulate and right posterior cingulate cortices both correlated inversely with the change of craving rating during stress imagery. CONCLUSIONS: The greater left frontolimbic activity in women suggests that women might use more verbal coping strategies than do men while experiencing stress. The results also suggest a distinct role of the cingulate cortices in modulating stress-induced cocaine craving.

Recent cannabis abuse decreased stress-induced BOLD signals in the frontal and cingulate cortices of cocaine dependent individuals.

Previous neuroimaging studies showed that use of marijuana can alter patterns of cortical activation during rest or a task challenge. We used functional magnetic resonance imaging to examine whether recent cannabis abuse contributed to stress-induced blood-oxygen-level-dependent (BOLD) contrast in a group of cocaine-dependent individuals. Emotional stress was induced using the script-guided imagery paradigm, in which subjects imagined being in a real-life stressful situation and, as a control, in a neutral situation, while BOLD signals of their brain were acquired with a 1.5 T scanner. Abstinent cocaine-dependent subjects with recent marijuana abuse (n=8) were compared with abstinent cocaine-dependent subjects who had not abused marijuana recently (n=18). The two groups were otherwise matched in their demographic characteristics and drug use history. All subjects were abstinent for at least 15 days and drug free as confirmed by urine drug screening before the imaging session. Recent cannabis abusers demonstrated hypo-activation in frontal cortical areas including the perigenual anterior cingulate during increased emotional stress. In contrast, at the same statistical threshold, no brain regions showed increased activation in recent cannabis abusers compared with non-abusers. The group difference in the perigenual anterior cingulate remained even when lifetime cocaine and alcohol consumption was accounted for in covariance analysis. These results provide evidence that recent cannabis abuse is associated with decreased activation in the frontal cortex during an emotional stress task. The results suggest an abnormal cognitive control mechanism during affective processing in association with heavy cannabis use.

Neuroimaging study of sex differences in the neuropathology of cocaine abuse.

BACKGROUND: Female and male substance abusers differ in their disease patterns and clinical outcomes. An important question in addiction neuroscience thus concerns the neural substrates underlying these sex differences. OBJECTIVE: This article aims to examine what is known of the neural mechanisms involved in the sex differences between substance abusers. METHODS: We reviewed neuroimaging studies that addressed sex differences in cerebral perfusion deficits after chronic cocaine use and in regional brain activation during pharmacologic challenge and cue-induced craving. We also present results from a preliminary study in which cocaine-dependent men and women participated in script-guided imagery of stress- and drug cue-related situations while blood oxygenation level-dependent signals of their brain were acquired in a 1.5T scanner. Spatial pre-processing and statistical analysis of brain images were performed. Regional brain activation was compared between stress and drug cue trials in men versus women. RESULTS: The results of our study showed greater activation in the left uncus and right claustrum (both, statistical threshold of P = 0.01, uncorrected; extent = 10 voxels) in men (n = 5) during drug cue trials compared with stress trials. No brain regions showed greater activation during stress trials compared with drug cue trials. In contrast, women (n = 6) showed greater activation in the right medial and superior frontal gyri during stress trials compared with drug cue trials at the same statistical threshold. No brain regions showed more activation during drug cue trials than during stress trials. CONCLUSIONS: The studies reviewed underscore the need to consider sex-related factors in examining the neuropathology of cocaine addiction. Our preliminary results also suggest important sex differences in the effect of stress- and drug cue-associated brain activation in individuals with cocaine use disorder.