Brain metabolic changes during cigarette craving

BACKGROUND: In functional brain imaging studies, exposure to cues related to cocaine, opiates, and alcohol in dependent individuals is associated with activation of the anterior cingulate gyrus, amygdala, orbitofrontal cortex, and dorsolateral prefrontal cortex. Craving for these substances positively correlates with activity in the orbitofrontal cortex, dorsolateral prefrontal cortex, and anterior insula. The objective of this study was to determine changes in regional cerebral glucose metabolism and correlations between craving and regional metabolism in heavy cigarette smokers exposed to cigarette-related cues. METHODS: Twenty heavy smokers (who smoked > or =20 cigarettes per day) and 20 nonsmoking control subjects underwent 2 fluorine 18-fluorodeoxyglucose positron emission tomography scans 10 days apart in randomized order: one while watching a videotape that presented cigarette-related cues and handling a cigarette, and the other while watching an educational (nature) videotape and handling a neutral object (pen). RESULTS: From the neutral to the cigarette cue scan, heavy smokers had greater increases than nonsmoking controls in relative glucose metabolism in the perigenual anterior cingulate gyrus spanning the midline. Significant positive correlations were found between intensity of craving and metabolism in the orbitofrontal cortex, dorsolateral prefrontal cortex, and anterior insula bilaterally. An unexpected positive association was found between craving and metabolism in the right sensorimotor cortex. CONCLUSIONS: Brain regions associated with arousal, compulsive repetitive behaviors, sensory integration, and episodic memory are activated during exposure to cigarette-related cues and cigarette craving. These regional brain activations and associations with craving are similar to findings with other addictive substances.     

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.     

Differential roles of the prefrontal cortical subregions and basolateral amygdala in compulsive cocaine seeking and relapse after voluntary abstinence in rats

Compulsive drug use and a persistent vulnerability to relapse are key features of addiction. Imaging studies have suggested that these features may result from deficits in prefrontal cortical structure and function, and thereby impaired top‐down inhibitory control over limbic–striatal mechanisms of drug‐seeking behaviour. We tested the hypothesis that selective damage to distinct subregions of the prefrontal cortex, or to the amygdala, after a short history of cocaine taking would: (i) result in compulsive cocaine seeking at a time when it would not usually be displayed; or (ii) facilitate relapse to drug seeking after abstinence. Rats with selective, bilateral excitotoxic lesions of the basolateral amygdala or anterior cingulate, prelimbic, infralimbic, orbitofrontal or anterior insular cortices were trained to self‐administer cocaine under a seeking–taking chained schedule. Intermittent mild footshock punishment of the cocaine‐seeking response was then introduced. No prefrontal cortical lesion affected the ability of rats to withhold their seeking responses. However, rats with lesions to the basolateral amygdala increased their cocaine‐seeking responses under punishment and were impaired in their acquisition of conditioned fear. Following a 7‐day abstinence period, rats were re‐exposed to the drug‐seeking environment for assessment of relapse in the absence of punishment or cocaine. Rats with prelimbic cortex lesions showed decreased seeking responses during relapse, whereas those with anterior insular cortex lesions showed an increase. Combined, these results show that acute impairment of prefrontal cortical function does not result in compulsive cocaine seeking after a short history of self‐administering cocaine, but further implicates subregions of the prefrontal cortex in relapse.     

Brain-stimulation reward, morphine-induced oral stereotypy, and sensitization: implications for abuse

Early professionals believed that it was unlikely that anyone but the emotionally unstable received pleasure and became addicted to narcotic drugs. This position was well entrenched and influenced much of the thinking well into the latter half of the last century. Although the discovery of a brain reward system was made early in the 1950's it was not until 20 years later that this discovery was applied to the study of the mechanisms involved in the rewarding aspects of abused substances. Along this vein results will be shown in which opiate antagonist block the dopamine agonist activation of the brain reward system as well as the corollary. Sensitization of the reward system suggests that a driving force for drug use is 'liking' and not just 'wanting.' Basal changes in cerebral metabolic rates of glucose are seen in the presence of cues associated with morphine experience, giving evidence for the role of drug related cues in craving. Finally we asked the question 'Do old rats have as much fun as young rats?'     

Individual differences in smoking-related cue reactivity in smokers: an eye-tracking and fMRI study

Measures of cue reactivity provide a means of studying and understanding addictive behavior. We wanted to examine the relationship between different cue reactivity measures, such as attentional bias and subjective craving, and functional brain responses toward smoking-related cues in smokers. We used eye-tracking measurements, a questionnaire for smoking urges-brief and functional magnetic resonance imaging to assess the responses to smoking-related and neutral visual cues from 25 male smokers after 36 h of smoking abstinence. Regression analyses were conducted to determine the correlation between cue-evoked brain responses and the attentional bias to smoking-related cues. The eye gaze dwell time percentage was longer in response to smoking-related cues than neutral cues, indicating significant differences in attentional bias towards smoking-related cues. The attentional bias to smoking-related cues correlated with subjective craving ratings (r=0.660, p<0.001). The dorsolateral prefrontal cortex, the putamen, the posterior cingulate cortex and the primary motor cortex were associated with the attentional bias to smoking-related cues, whereas the orbitofrontal cortex, the insula and the superior temporal gyrus were associated with smoking-related cue-induced craving and smoking urges. These results suggest that attentional mechanisms in combination with motivational and reward-related mechanisms play a role in smoking-related cue reactivity. We confirmed a positive correlation between different smoking-related cue reactivities, such as attentional bias and subjective craving, and functional brain responses in various individuals. Further studies in this field might contribute to a better individualized understanding of addictive behavior.     

Dopaminergic dysfunction in alcoholism and schizophrenia--psychopathological and behavioral correlates.

Dysfunction of central dopaminergic neurotransmission has been implicated in the pathogenesis of schizophrenia as well as drug and alcohol dependence. Different drugs of abuse stimulate dopamine release in the ventral striatum and thus reinforce drug consumption. Increased subcortical dopamine release has also been associated with the pathogenesis of positive symptoms in schizophrenia and may be driven by a prefrontal dopaminergic dysfunction. These seemingly heterogeneous findings may be explained by recent research in non-human primates. According to these studies, reward anticipation but not anticipated reward consumption is accompanied by a phasic dopamine release in the striatum and prefrontal cortex. In the striatum, phasic dopamine release primarily affects motivation, psychomotor activation and reward craving, while in the prefrontal cortex, dopaminergic stimulation is involved in the activation of working memory and reward anticipation. In alcoholism, previously neutral stimuli that have been associated with alcohol intake can become conditioned cues which activate phasic dopamine release and reward craving. In schizophrenia, stress-induced or chaotic activation of dopamine release may attribute incentive salience to otherwise irrelevant stimuli and thus be involved in the pathogenesis of delusional mood and other positive symptoms. Studies in humans and non-human primates emphasize the role of dopaminergic neurotransmission in reward anticipation and its dysfunction in different neuropsychiatric diseases.     

Drug addiction and its underlying neurobiological basis: neuroimaging evidence for the involvement of the frontal cortex

OBJECTIVE: Studies of the neurobiological processes underlying drug addiction primarily have focused on limbic subcortical structures. Here the authors evaluated the role of frontal cortical structures in drug addiction. METHOD: An integrated model of drug addiction that encompasses intoxication, bingeing, withdrawal, and craving is proposed. This model and findings from neuroimaging studies on the behavioral, cognitive, and emotional processes that are at the core of drug addiction were used to analyze the involvement of frontal structures in drug addiction. RESULTS: The orbitofrontal cortex and the anterior cingulate gyrus, which are regions neuroanatomically connected with limbic structures, are the frontal cortical areas most frequently implicated in drug addiction. They are activated in addicted subjects during intoxication, craving, and bingeing, and they are deactivated during withdrawal. These regions are also involved in higher-order cognitive and motivational functions, such as the ability to track, update, and modulate the salience of a reinforcer as a function of context and expectation and the ability to control and inhibit prepotent responses. CONCLUSIONS: These results imply that addiction connotes cortically regulated cognitive and emotional processes, which result in the overvaluing of drug reinforcers, the undervaluing of alternative reinforcers, and deficits in inhibitory control for drug responses. These changes in addiction, which the authors call I-RISA (impaired response inhibition and salience attribution), expand the traditional concepts of drug dependence that emphasize limbic-regulated responses to pleasure and reward.     

Correlation Between Ventromedial Prefrontal Cortex Activation to Food Aromas and Cue-Driven Eating: An fMRI Study

Food aromas are signals associated with both food's availability and pleasure. Previous research from this laboratory has shown that food aromas under fasting conditions evoke robust activation of medial prefrontal brain regions thought to reflect reward value (Bragulat et al., Obesity (Silver Spring), 18(8): 1566?C1571, 2010). In the current study, 18 women (11 normal weight and 7 obese) underwent a 2-day imaging study (one after being fed and one while fasting). All were imaged on a 3T Siemens Trio-Tim scanner while sniffing two food (F; pasta and beef) odors, one non-food (NF; Douglas fir) odor, and an odorless control (CO). Prior to imaging, participants rated hunger and perceived odor qualities and completed the Dutch Eating Behavior Questionnaire (DEBQ) to assess "externality" (the extent to which eating is driven by external food cues). Across all participants, both food and non-food odors (compared to CO) elicited large blood oxygenation level dependent (BOLD) responses in olfactory and reward-related areas, including the medial prefrontal and anterior cingulate cortex, bilateral orbitofrontal cortex, and bilateral piriform cortex, amygdala, and hippocampus. However, food odors produced greater activation of medial prefrontal cortex, left lateral orbitofrontal cortex, and inferior insula than non-food odors. Moreover, there was a significant correlation between the (F?>?CO) BOLD response in ventromedial prefrontal cortex and ??externality?? sub-scale scores of the DEBQ, but only under the fed condition; no such correlation was present with the (NF?>?CO) response. This suggests that in those with high externality, ventromedial prefrontal cortex may inappropriately valuate external food cues in the absence of internal hunger.     

Frontolimbic brain abnormalities in patients with borderline personality disorder: a volumetric magnetic resonance imaging study.

BACKGROUND: Dual frontolimbic brain pathology has been suggested as a possible correlate of impulsivity and aggressive behavior. One previous study reported volume loss of the hippocampus and the amygdala in patients with borderline personality disorder. We measured limbic and prefrontal brain volumes to test the hypothesis that frontolimbic brain pathology might be associated with borderline personality disorder. METHODS: Eight unmedicated female patients with borderline personality disorder and eight matched healthy controls were studied. The volumes of the hippocampus, amygdala, and orbitofrontal, dorsolateral prefrontal, and anterior cingulate cortex were measured in the patients using magnetic resonance imaging volumetry and compared to those obtained in the controls. RESULTS: We found a significant reduction of hippocampal and amygdala volumes in borderline personality disorder. There was a significant 24% reduction of the left orbitofrontal and a 26% reduction of the right anterior cingulate cortex in borderline personality disorder. Only left orbitofrontal volumes correlated significantly with amygdala volumes. CONCLUSIONS: While volume loss of a single brain structure like the hippocampus is quite an unspecific finding in neuropsychiatry, the patterns of volume loss of the amygdala, hippocampus, and left orbitofrontal and right anterior cingulate cortex might differentiate borderline personality disorder from other neuropsychiatric conditions.     

Cortical and Sub-Cortical Effects in Primate Models of Cocaine Use: Implications for Addiction and the Increased Risk of Psychiatric Illness

Drug abuse is a serious risk factor for the incidence and severity of multiple psychiatric illnesses. Understanding the neurobiological consequences of repeated exposure to abused drugs can help to inform how those risks are manifested in terms of specific neurochemical mechanisms and brain networks. This review examines selective studies in non-human primates that employed a cocaine self-administration model. Neurochemical consequences of chronic exposure appear to differ from observations in rodent studies. Whereas chronic intermittent exposure in the rodent is usually associated with a dose-dependent increase in dopaminergic response to a cocaine challenge, in the rhesus monkey, high cumulative exposure was not observed to cause a sensitized dopamine response. These non-human primate observations are concordant with clinical findings in human users. The results of cue exposure studies on dopaminergic transmission are also reviewed. Direct microdialysis measurements indicate that there is not a sustained increase in dopamine associated with cocaine-linked cues. As an alternative to striatal dopaminergic mechanisms mediating cue effects, single unit studies in prefrontal cortex during self-administration in monkeys suggests the orbitofrontal and anterior cingulate cortex are strongly engaged by cocaine cues. Based on the strong clinical imaging literature on cortical and cognitive dysfunction associated with addiction, it is proposed that the strong engagement of cortical systems during repeated cocaine reinforcement results in maladaptive changes that contribute to the risks of drug use for exacerbation of other psychiatric disorders.     

Correlation between dopamine D(2) receptors in the ventral striatum and central processing of alcohol cues and craving

OBJECTIVE: Alcohol and other drugs of abuse stimulate dopamine release in the ventral striatum, which includes the nucleus accumbens, a core region of the brain reward system, and reinforce substance intake. Chronic alcohol intake is associated with down-regulation of central dopamine D(2) receptors, and delayed recovery of D(2) receptor sensitivity after detoxification is positively correlated with high risk for relapse. Prolonged D(2) receptor dysfunction in the ventral striatum may interfere with a dopamine-dependent error detection signal and bias the brain reward system toward excessive attribution of incentive salience to alcohol-associated stimuli. METHOD: Multimodal imaging, with the radioligand [(18)F]desmethoxyfallypride and positron emission tomography as well as functional magnetic resonance imaging (fMRI), was used to compare 11 detoxified male alcoholics with 13 healthy men. The authors measured the association of D(2)-like dopamine receptors in the ventral striatum with alcohol craving and central processing of alcohol cues. RESULTS: Activation of the medial prefrontal cortex and striatum by alcohol-associated stimuli, relative to activation by neutral visual stimuli, was greater in the detoxified alcoholics than in the healthy men. The alcoholics displayed less availability of D(2)-like receptors in the ventral striatum, which was associated with alcohol craving severity and with greater cue-induced activation of the medial prefrontal cortex and anterior cingulate as assessed with fMRI. DISCUSSION: In alcoholics, dopaminergic dysfunction in the ventral striatum may attribute incentive salience to alcohol-associated stimuli, so that alcohol cues elicit craving and excessive activation of neural networks associated with attention and behavior control.     

Insights from recent positron emission tomographic studies of drug abuse and dependence

PURPOSE OF REVIEW: Recent positron emission tomographic studies demonstrate a variety of abnormalities in the brains of addicted individuals. This review aims to discuss and highlight these findings. RECENT FINDINGS: The recent findings are as follows: (a) the reward response to an addictive substance is associated with increased dopamine release in the striatum. (b) Activation of the orbitofrontal region is involved in the reinforcing properties of a drug. (c) Behavioral, cognitive and affective abnormalities are associated with alterations in specific brain networks and regions (e.g., prefrontal cortices) in drug abusers. (d) Personality traits may play a role in the susceptibility to addiction and the brain's responses to drugs. (e) Sex-differences exist for cue-induced craving. (f) Several studies have confirmed decreased D2 receptors in drug users, which is associated with increased salience to drug cues. (g) Serotonergic transporters are decreased in the current users of 3,4-methylene-deoxy-methamphetamine but found normal in the past users of 3,4-methylene-deoxy-methamphetamine. SUMMARY: Abnormalities in the dopaminergic, opioid, and serotonergic systems in drug abusers are seen in positron emission tomography scans. Decreased D2 receptor densities in drug users, whether premorbid or the consequence of substance misuse, imply a source of the susceptibility to relapse of this population. Insights from these studies could lead to better treatment approaches targeting specific neurotransmitter systems.     

Neuroanatomical and neurochemical bases of theory of mind

This paper presents a novel neurobiological model of theory of mind (ToM) that incorporates both neuroanatomical and neurochemical levels of specificity. Within this model, cortical and subcortical regions are functionally organized into networks that subserve the ability to represent cognitive and affective mental states to both self and other. The model maintains that (1) cognitive and affective aspects of ToM are subserved by dissociable, yet interacting, prefrontal networks. The cognitive ToM network primarily engages the dorsomedial prefrontal cortex, the dorsal anterior cingulate cortex and the dorsal striatum; and the affective ToM network primarily engages the ventromedial and orbitofrontal cortices, the ventral anterior cingulate cortex, the amygdala and the ventral striatum; (2) self and other mental-state representation is processed by distinct brain regions within the mentalizing network, and that the ability to distinguish between self and other mental states is modulated by a functionally interactive dorsal and ventral attention/selection systems at the temporoparietal junction and the anterior cingulate cortex; and (3) ToM functioning is dependent on the integrity of the dopaminergic and serotonergic systems which are primarily engaged in the maintenance and application processes of represented mental states. In addition to discussing the mechanisms involved in mentalizing in terms of its component processes, we discuss the model's implications to pathologies that variably impact one's ability to represent, attribute and apply mental states.     

Reward sensitivity modulates connectivity among reward brain areas during processing of anticipatory reward cues

Reward sensitivity, or the tendency to engage in motivated approach behavior in the presence of rewarding stimuli, may be a contributory factor for vulnerability to disinhibitory behaviors. Although evidence exists for a reward sensitivity‐related increased response in reward brain areas (i.e. nucleus accumbens or midbrain) during the processing of reward cues, it is unknown how this trait modulates brain connectivity, specifically the crucial coupling between the nucleus accumbens, the midbrain, and other reward‐related brain areas, including the medial orbitofrontal cortex and the amygdala. Here, we analysed the relationship between effective connectivity and personality in response to anticipatory reward cues. Forty‐four males performed an adaptation of the Monetary Incentive Delay Task and completed the Sensitivity to Reward scale. The results showed the modulation of reward sensitivity on both activity and functional connectivity (psychophysiological interaction) during the processing of incentive cues. Sensitivity to reward scores related to stronger activation in the nucleus accumbens and midbrain during the processing of reward cues. Psychophysiological interaction analyses revealed that midbrain–medial orbitofrontal cortex connectivity was negatively correlated with sensitivity to reward scores for high as compared with low incentive cues. Also, nucleus accumbens–amygdala connectivity correlated negatively with sensitivity to reward scores during reward anticipation. Our results suggest that high reward sensitivity‐related activation in reward brain areas may result from associated modulatory effects of other brain regions within the reward circuitry.     

基于独立成分分析方法的海洛因成瘾者功能磁共振成像研究

目的 使用独立成分分析(ICA)法分析功能磁共振(fMRI)数据研究线索诱导因素导致海洛因成瘾者复吸的神经网络. 方法 安徽医科大学附属省立医院神经外科自2010年2月至2010年12月对海洛因成瘾组(n=15,来自安徽省戒毒康复中心)和正常对照组(n=15,来自招募的志愿者)在接受吸毒相关场景视频刺激的同时进行fMRI扫描,然后使用ICA方法对数据进行分析和比较2组受试者脑区的激活情况. 结果 与正常对照组相比,海洛因成瘾组患者双侧前额叶、左前扣带回、双侧后扣带回、左侧顶叶、左侧颞下回的激活降低;双侧伏核、右侧海马以及部分枕叶的激活增强,差异有统计学意义(P＜0.05). 结论 ICA方法是一种有效的任务相关fMRI数据分析方法,海洛因成瘾者学习记忆和奖赏系统相关脑区功能改变是线索诱发复吸的重要原因,主要涉及左前额叶、左顶叶、前后扣带回、海马、伏核等脑区.     

Mood disturbances and regional cerebral metabolic abnormalities in recently abstinent methamphetamine abusers

BACKGROUND: Mood disturbances in methamphetamine (MA) abusers likely influence drug use, but the neurobiological bases for these problems are poorly understood. OBJECTIVE: To assess regional brain function and its possible relationships with negative affect in newly abstinent MA abusers. DESIGN: Two groups were compared by measures of mood and cerebral glucose metabolism ([18F]fluorodeoxyglucose positron emission tomography) during performance of a vigilance task. SETTING: Participants were recruited from the general community to a research center. PARTICIPANTS: Seventeen abstaining (4-7 days) MA abusers (6 women) were compared with 18 control subjects (8 women). MAIN OUTCOME MEASURES: Self-reports of depressive symptoms and anxiety were measured, as were global and relative glucose metabolism in the orbitofrontal, cingulate, lateral prefrontal, and insular cortices and the amygdala, striatum, and cerebellum. RESULTS: Abusers of MA provided higher self-ratings of depression and anxiety than control subjects and differed significantly in relative regional glucose metabolism: lower in the anterior cingulate and insula and higher in the lateral orbitofrontal area, middle and posterior cingulate, amygdala, ventral striatum, and cerebellum. In MA abusers, self-reports of depressive symptoms covaried positively with relative glucose metabolism in limbic regions (eg, perigenual anterior cingulate gyrus and amygdala) and ratings of state and trait anxiety covaried negatively with relative activity in the anterior cingulate cortex and left insula. Trait anxiety also covaried negatively with relative activity in the orbitofrontal cortex and positively with amygdala activity. CONCLUSIONS: Abusers of MA have abnormalities in brain regions implicated in mood disorders. Relationships between relative glucose metabolism in limbic and paralimbic regions and self-reports of depression and anxiety in MA abusers suggest that these regions are involved in affective dysregulation and may be an important target of intervention for MA dependence.     

Common and distinct networks underlying reward valence and processing stages: a meta-analysis of functional neuroimaging studies

To better understand the reward circuitry in human brain, we conducted activation likelihood estimation (ALE) and parametric voxel-based meta-analyses (PVM) on 142 neuroimaging studies that examined brain activation in reward-related tasks in healthy adults. We observed several core brain areas that participated in reward-related decision making, including the nucleus accumbens (NAcc), caudate, putamen, thalamus, orbitofrontal cortex (OFC), bilateral anterior insula, anterior cingulate cortex (ACC) and posterior cingulate cortex (PCC), as well as cognitive control regions in the inferior parietal lobule and prefrontal cortex (PFC). The NAcc was commonly activated by both positive and negative rewards across various stages of reward processing (e.g., anticipation, outcome, and evaluation). In addition, the medial OFC and PCC preferentially responded to positive rewards, whereas the ACC, bilateral anterior insula, and lateral PFC selectively responded to negative rewards. Reward anticipation activated the ACC, bilateral anterior insula, and brain stem, whereas reward outcome more significantly activated the NAcc, medial OFC, and amygdala. Neurobiological theories of reward-related decision making should therefore take distributed and interrelated representations of reward valuation and valence assessment into account.     

Brain activities associated with gaming urge of online gaming addiction

The aim of this study was to identify the neural substrates of online gaming addiction through evaluation of the brain areas associated with the cue-induced gaming urge. Ten participants with online gaming addiction and 10 control subjects without online gaming addiction were tested. They were presented with gaming pictures and the paired mosaic pictures while undergoing functional magnetic resonance imaging (fMRI) scanning. The contrast in blood-oxygen-level dependent (BOLD) signals when viewing gaming pictures and when viewing mosaic pictures was calculated with the SPM2 software to evaluate the brain activations. Right orbitofrontal cortex, right nucleus accumbens, bilateral anterior cingulate and medial frontal cortex, right dorsolateral prefrontal cortex, and right caudate nucleus were activated in the addicted group in contrast to the control group. The activation of the region-of-interest (ROI) defined by the above brain areas was positively correlated with self-reported gaming urge and recalling of gaming experience provoked by the WOW pictures. The results demonstrate that the neural substrate of cue-induced gaming urge/craving in online gaming addiction is similar to that of the cue-induced craving in substance dependence. The above-mentioned brain regions have been reported to contribute to the craving in substance dependence, and here we show that the same areas were involved in online gaming urge/craving. Thus, the results suggest that the gaming urge/craving in online gaming addiction and craving in substance dependence might share the same neurobiological mechanism.     

The neural correlates of cue-induced craving in cocaine-dependent women

OBJECTIVE: Drug use reminders are associated with localized changes in brain activity related to intense drug wanting or craving in cocaine-dependent men. While cocaine dependence is prevalent and disabling in women, and certain clinically relevant sex differences exist, there is an absence of knowledge related to the neural correlates of cocaine craving in cocaine-dependent women. METHOD: The differential neural response to imagery depicting cocaine use and neutral imagery was defined by using [15O]H2O positron emission tomography (PET) imaging in eight cocaine-dependent women. Results were compared with a matched group of eight cocaine-dependent men. RESULTS: Cocaine-related imagery was associated with relative increases in cocaine craving and increases in regional cerebral blood flow in the superior temporal gyrus, dorsal anterior and posterior cingulate cortex, nucleus accumbens area, and the central sulcus. Compared with the results of an identical PET study in matched cocaine-dependent men, conditioned cocaine craving in women was associated with less activation of the amygdala, insula, orbitofrontal cortex, and ventral cingulate cortex and greater activation of the central sulcus and widely distributed frontal cortical areas. CONCLUSIONS: These findings suggest the presence of sex differences in the functional anatomy of cue-induced cocaine craving associated with drug dependence. Such differences may reflect sex differences in conditioned associations to cocaine use, in affective and other corollaries of cocaine craving, or in their volitional regulation and may underlie apparent sex differences in the effects of cocaine abstinence and the expectations of treatment outcome. Some support for the need for sex-specific strategies for treatment of cocaine dependence is also furnished by the findings of this study.