Investigation of brain electrophysiological properties among heroin addicts: Quantitative EEG and event‐related potentials

This study aims to introduce a new approach of a comprehensive paradigm to evaluate brain electrophysiological properties among addicts. Electroencephalographic spectral power as well as amplitudes and latencies of mismatch negativity (MMN), P300, and P600 components were evaluated among 19 male heroin addicts and 19 healthy nonsmoker subjects using a paradigm consisting of three subparadigms, namely (1) digit span Wechsler test, (2) auditory oddball, and (3) visual cue‐reactivity oddball paradigms. Task 1 provided auditory P300 and P600 in association with working memory. Task 2 provided auditory P300 as well as small and large deviant MMN event‐related potential (ERPs). Finally, task 3 provided visual cue‐reactivity P300. Results show that beta power was higher among heroin addicts while delta, theta, and alpha powers were decreased compared with healthy subjects. ERP analysis confirmed the decline of brain‐evoked potential amplitudes when compared with healthy subjects, thus indicating a broad neurobiological vulnerability of preattentive and attentional processing including attentional deficits and compromise of discrimination abilities. The prolonged latency of ERPs reflects poor cognitive capacity in the engagement of attention and memory resources. On the other hand, an increase of attention towards the heroin‐related stimuli could be concluded from the increase of P300 in the cue‐reactivity condition among heroin addicts. Findings suggest that applying this paradigm in addiction studies benefits comprehensive evaluation of neuroelectrophysiological activity among addicts, which can promote a better understanding of drugs' effects on the brain as well as define new neuroelectrophysiological characteristics of addiction properties. © 2016 Wiley Periodicals, Inc.     

EEG spectral power and mean frequencies in early heroin abstinence

The purpose of the present study was to investigate cumulative heroin effects on brain functioning by studying relationships among electroencephalography (EEG) spectral power and mean frequencies and heroin abuse history. Eyes-closed resting EEG data were collected from the 19 monopolar electrode sites in 33 heroin abusers and 13 age-matched healthy volunteers. The mean age of the patients was 23.1+/-4.5 years, the duration of daily heroin abuse (DDHA) ranged from 4 to 44 months, the intravenous doses of heroin ranged from 0.04 to 1.00 g/day, the abstinence length ranged from 6 days to 4.5 months. General linear model (GLM) repeated measures procedure revealed a significant group effect on the distribution of the mean power spectrum between bands and mean frequencies in almost all analyzed derivations. Further analysis demonstrated that these intergroup differences were diversely related to at least three aspects of heroin-taking history. Frequency shifts in alpha2 range, most prominent in frontal and central derivations, were related to duration of daily heroin consumption. Slowing of alpha1 mean frequency, most prominent in central, temporal, and occipital derivations, was registered mainly in heroin addicts who abused high doses of the drug. Spectral power characteristics of brain electrical activities in our patient population were strongly predicted by abstinence length. The present results give grounds to suppose that chronic heroin-taking induces neuronal oscillation frequency changes, which may contribute to the development of antisocial trends and some semantic processes disturbances in these patients. Supplementary neurophysiological deficit is characteristic for heroin addicts who takes high doses of the drug, however, its relation to heroin abuse remains unclear. Pronounced desynchronization is observed in acute heroin withdrawal, and spectral power characteristics tend to normalize almost completely during several weeks of abstinence.     

Abnormal resting‐state functional connectivity of the nucleus accumbens in multi‐year abstinent heroin addicts

Functional neuroimaging studies suggest that abnormal brain functional connectivity may be the neural underpinning of addiction to illicit drugs and of relapse after successful cessation therapy. Aberrant brain networks have been demonstrated in addicted patients and in newly abstinent addicts. However, it is not known whether abnormal brain connectivity patterns persist after prolonged abstinence. In this cross‐sectional study, whole‐brain resting‐state functional magnetic resonance images (8 min) were collected from 30 heroin‐addicted individuals after a long period of abstinence (more than 3 years) and from 30 healthy controls. We first examined the group differences in the resting‐state functional connectivity of the nucleus accumbens (NAc), a brain region implicated in relapse‐related processes, including craving and reactivity to stress following acute and protracted withdrawal from heroin. We then examined the relation between the duration of abstinence and the altered NAc functional connectivity in the heroin group. We found that, compared with controls, heroin‐dependent participants exhibited significantly greater functional connectivity between the right ventromedial prefrontal cortex and the NAc and weaker functional connectivity between the NAc and the left putamen, left precuneus, and supplementary motor area. However, with longer abstinence time, the strength of NAc functional connectivity with the left putamen increased. These results indicate that dysfunction of the NAc functional network is still present in long‐term‐abstinent heroin‐dependent individuals. © 2015 Wiley Periodicals, Inc.     

Do obsessive-compulsive patients and abstinent heroin addicts share a common psychophysiological mechanism?

BACKGROUND/AIM: Working memory (WM) and attentional deficits have been implicated in the pathophysiology of both obsessive-compulsive disorder (OCD) and opioid addiction. The P300 component of event-related potentials (ERPs) is considered as an index of on-line updating of WM and/or attentional operations involved in this function. The present study aimed at comparing the P300 elicited during a WM test in patients with prolonged heroin abstinence, those with OCD and healthy controls, in order to demonstrate possibly common underlying psychophysiological mechanisms. METHODS: The P300 component was evaluated during the anticipatory period of a WM test in 20 patients characterized by a past history of opioid dependence (6 months abstinence), in 18 OCD patients, and 20 healthy subjects matched for age, sex and educational level. RESULTS: The two patient groups showed a considerable reduction of the P300 amplitudes, located at the right frontal area as compared with healthy controls. The abstinent heroin addicts exhibited a significantly lower P300 amplitude at central frontal areas and a significantly higher P300 amplitude at the left occipital region relative to the other two groups. Furthermore, the abstinent group showed a notable delay of P300 latency relative to controls and OCD patients at the right occipital region. Moreover, the OCD patients manifested a significant prolongation of P300 located at the central prefrontal area, relative to addicts and healthy controls. CONCLUSIONS: These findings point to considerable WM and/or attentional deficits in the long-term abstinent syndrome of heroin misuse and OCD associated with distributed and prefrontal cortical circuits, respectively. Furthermore, the present findings suggest that both OCD and long-term abstinent heroin addicts may share a common impairment of WM and/or attention involving or affecting the right prefrontal areas.     

Pituitary-gonadal function in heroin addicts.

The present study deals with pituitary-gonadal function in male heroin addicts, 6 patients with schizophrenia and 31 with mild personality disorders. We examined the serum follicle-stimulating hormone (FSH), luteinizing hormone (LH) and testosterone levels at the moment of hospitalization (at the maximum of heroin addiction), and 48 h and 10 days later. FSH levels were definitely reduced in all the patients and did not change during the period of heroin withdrawal. The LH levels were reduced to a lesser extent, but significantly, and did not change after 10 days of abstinence from the drug. Testosterone levels were very low and increased in the schizophrenics during withdrawal, but not in the other addicts. The possible influence of heroin addiction on catecholamine metabolism in the central nervous system and, therefore, on the hypothalamic releasing factor and pituitary gonadotrophins, and the peripheral effect on testicular function are discussed.     

Long-term abstinence syndrome in heroin addicts: indices of P300 alterations associated with a short memory task

Attentional deficits have been implicated in the pathophysiology of opioid addicts. The P300 component of event-related potentials (ERPs) is considered as a manifestation of attentional operations. The authors' goal was the comparison of P300 elicited during a short memory test between subjects with prolonged heroin abstinence and current heroin users as well as healthy controls. The P300 component was evaluated during the anticipatory period of a short memory task in 20 patients characterized by a past history of opioid dependence (6 months abstinence), in 18 current heroin users and in 20 healthy comparison subjects, matched for age, sex and educational level. Abstinent heroin addicts exhibited significant reduction of P300 amplitude at central frontal region, relative to the other two groups. The findings are discussed in connection to the aim of identifying psychophysiological indices, addressing issues in opioid use disorders, and suggest that knowledge about cognitive operations, such as those reflected by P300 component, could provide further insight into psychophysiological mechanisms underlying the long-term abstinence state of heroin addicts.     

海洛因成瘾者脑电图的Walsh定量分析

目的：了解海洛因成瘾者脑电信号的高频段改变。方法：对32例海洛因成瘾者戒毒前后及对照组的脑电信号进行了有限Walsh变换分析及统计分析。结果：在δ、θ、α、γ和64－127Hz频段上多导联上可见功率改变。结论：戒毒之初过度抑制和过度警醒同存，在戒毒完成后脑觉醒度依然比常人为低，但高频段的功率减少持续存在。这一脑电图特征可能涉及精神依赖的生物学基础。     

Effect of sulpiride on chronic abstinence syndrome in addicted patients

A total of 410 patients (342 men and 68 women) addicted to heroin for at least 38 months, with or without previous methadone treatment experience, were treated with sulpiride before the appearance of withdrawal syndrome. The drug was injected intramuscularly in a single administration at a dosage of 600 mg. Successively, sulpiride was injected intramuscularly at a dosage of 200 mg 3 times per day from days 2-21 of hospitalization, and then at a dosage of 100 and 50 mg 3 times per day (days 22-25 and 26-29, respectively). All patients showed a suppression of withdrawal signs and symptoms within 6 days of treatment, as assessed by subjective and objective scores. The effect of sulpiride was compared with that of placebo administered to a control group of 10 heroin addicts. Because prolactin has been shown to reduce the dependence of rats to heroin and the naloxone-precipitated withdrawal syndrome in morphine-addicted animals, the effects of sulpiride on heroin addiction may be related to the hyperprolactinemic action of this drug.     

Abnormal P600 in heroin addicts with prolonged abstinence elicited during a working memory test.

The P600 component of event-related potentials, believed to be generated by anterior cingulate gyrus and basal ganglia, is considered as an index of aspects of second-pass parsing processes of information processing, having much in common with working memory (WM) systems. Moreover, dysfunction of these brain structures as well as WM deficits have been implicated in the pathophysiology of opioid addicts. The present study is focused on P600 elicited during a WM test in twenty heroin addicts with prolonged abstinence compared with an equal number of healthy controls. The results showed significantly prolonged latencies at right hemisphere, specifically at Fp2 abduction. Moreover, memory performance of patients did not differ from that of normal controls. These findings may indicate that abstinent heroin addicts manifest abnormal aspects of second-pass parsing processes as are reflected by the P600 latencies, elicited during a WM test. Additionally, the P600 might serve as a valuable investigative tool for a more comprehensive understanding of the neurobiological substrate of drug abuse.     

Rhabdomyolysis and concomitant neurological lesions after intravenous heroin abuse.

Seven cases of rhabdomyolysis in heroin addicts are presented. All patients showed concomitant neurological symptoms suggesting mononeuropathy, incomplete plexus lesions or myelopathy. In most cases rhabdomyolysis occurred without preceding trauma to the muscles (for example tissue compression or coma). Five patients had a history of recently resumed heroin abuse after prolonged abstinence. An allergic or toxic reaction to heroin or adulterants seems to be more likely than trauma in the pathogenesis of these complications. Severe rhabdomyolysis can occur without visible muscular swelling. Routine screening of creatine kinase is recommended in heroin addicts with neurological complications, as rhabdomyolysis may lead to fatal renal failure and may easily fail to be diagnosed.     

美沙酮联用丁丙诺啡对海洛因依赖重度药瘾戒毒治疗临床研究

目的　探索对海洛因依赖重度药瘾较理想的戒毒治疗方法。　　方法　采用美沙酮与丁丙诺啡联合用药方案 ,对海洛因依赖重度药瘾 41例行戒毒治疗 ,1 2天为一疗程 ,并与单用美沙酮组 2 0例进行比较。　　结果　联合用药组控制症状较彻底 ,鸦片类药物戒断症状量表 (OWS)总分平稳下降 ,症状波动小 ,减药顺利 ,两药替换平稳 ,戒毒成功率 73 2 %。　　结论　我们认为美沙酮联用丁丙诺啡是一种值得推荐的戒毒治疗方法。     

Attentional Bias to Drug- and Stress-Related Pictorial Cues in Cocaine Addiction Comorbid with Posttraumatic Stress Disorder

Introduction. Cocaine addiction places a specific burden on mental health services through its comorbidity with other psychiatric disorders. Treatment of patients with cocaine abuse is more complicated when addiction is co-occurring with posttraumatic stress disorder (PTSD). This study used dense-array event-related potential (ERP) technique to investigate whether the patients with this form of dual diagnosis display excessive reactivity to both trauma and drug cues as compared to neutral cues. Cue reactivity refers to a phenomenon in which individuals with a history of drug dependence exhibit verbal, physiological, and behavioral responses to cues associated with their preferred substance of abuse. This study explores ERP differences associated with cue-related responses to both drug and trauma cues in a three-category oddball task using neutral, drug-related, and trauma-related pictorial stimuli.

Methods. The study was conducted on 14 cocaine dependent participants, 11 participants with cocaine-dependence comorbid with PTSD, and 9 age- and gender-matched control subjects. A 128-channel Electrical Geodesics EEG system was used to record ERP during the visual three-category oddball task with three categories (neutral, drug, stress) of affective pictures.

Results. Patients with cocaine dependence and PTSD, as compared to patients with only cocaine addiction and control participants, showed excessive cue reactivity to both drug- and trauma-related visual stimuli. Most profound differences were found in the amplitude and latency of frontal P3a, and centro-parietal P3b ERP components. Group differences were found as well between patients with cocaine abuse (both addiction-only and dual diagnosis groups) versus controls on most ERP measures for drug-related cues.

Conclusion. We propose that the employed ERP cue reactivity variables could be used as valuable functional outcome measures in dually diagnosed drug addicts undergoing behavioral treatment.     

Transcutaneous electrical stimulation with Limoge current potentiates morphine analgesia and attenuates opiate abstinence syndrome

Transcutaneous electrostimulation is a somewhat controversial technique used in the management of the opiate withdrawal syndrome. We report an animal study of a particular transcutaneous electrostimulation called transcutaneous cranial electrostimulation, based on a technique used for many years on heroin addicts for the rapid severance of their addiction, which has been validated in a clinical setting by a double-blind trial. This technique involves the application of an intermittent high-frequency current (Limoge's current). Our experimental data show that this transcutaneous cranial electrostimulation increases morphine analgesia by threefold on the tail flick latency measure and produces a 48% attenuation of the abstinence syndrome observed after abrupt cessation of morphine administration. These results were obtained using a double-blind paradigm.     

Polyradiculoneuropathy associated with heroin abuse.

Neurological complications of heroin addiction have occurred only sporadically in the United Kingdom. We report the case of a young female patient who developed an acute polyradiculoneuropathy when she recommended intravenous heroin after four years abstinence. Another possible aetiological factor was a preceding flu-like illness but, after full investigations, we concluded that heroin abuse was the most likely cause of the neurological symptoms.     

Maintenance treatment of opiate addicts

Maintenance treatment is now the most common treatment of opiate addicts in Germany. The principle of maintenance treatment is the administration of an opioid in order to suppress withdrawal symptoms and heroin craving. In this manner, maintenance treatment successfully reduces heroin abuse and directly associated risk behaviour. Only a minority of maintenance patients became opiate abstinent (including the maintenance drug). Racemic methadone is the most extensively evaluated maintenance drug. A differential indication between medical opioids has not been scientifically established. According to the German regulations psychosocial support is an obligatory part of maintenance treatment. Most opiate addicts suffer from comorbid mental and somatic diseases. Therefore psychiatric and somatic treatment is indicated and of proven value.     

Electroencephalographic power and coherence analyses suggest altered brain function in abstinent male heroin-dependent patients

Previous studies have shown that drug abuse is associated with altered brain function. However, studies of heroin abuse-related brain dysfunctions are scarce. Electroencephalographic (EEG) power and coherence analyses are two important tools for examining the effects of drugs on brain function. In the present study, we compared EEG power and coherence measures of 18 abstinent heroin-dependent subjects with those of 12 healthy control subjects. Furthermore, within the heroin group, associations between heroin use in the past, heroin craving and these EEG measures were studied. The results show that heroin-dependent subjects have increased relative beta-2 power and increased left intrahemispheric gamma coherence compared with control subjects. Furthermore, coherence measures showed correlations with clinical variables. These EEG abnormalities may reflect underlying changes in brain function due to long-term drug abuse and premorbid characteristics.     

海洛因依赖者环境线索诱发心理生理反应

目的：了解海洛因依赖者对吸毒相关环境线索诱发反应。方法：对来自自愿戒毒机构的36例刚完成生理脱毒（康复早期）的海洛因依赖者和劳教戒毒机构112例康复期满1年的海洛因依赖者观看吸毒相关视频同时给予海洛因模拟物及吸毒用具刺激,于暴露前后自评渴求程度、情绪以及戒断症状反应;用生物反馈仪自动记录暴露前后的生理反应。结果：环境线索暴露后海洛因依赖者心理渴求、害怕／焦虑、抑郁／悲伤、戒断症状、心率、皮肤导电和肌电增高（P〈0．05）,中性／放松／自然降低（P〈0．05）。自愿戒毒机构康复早期海洛因依赖者环境诱发心率增高,比康复期满一年以上者更明显（P〈0．05）,其余与康复期长短无显著关系。结论：海洛因依赖者戒断康复期的延长并不会使渴求和环境诱发心理生理反应减弱或消褪。     

长期海洛因成瘾者前额叶功能连接的静息态fMRI研究

目的 利用静息态fMRI探讨长期海洛因成瘾者前额叶功能连接的变化情况.方法 13例长期海洛因成瘾者和14例正常者接受静息态fMRI检查,对数据进行相关的预处理后,以前额叶为种子点与全脑每个体素进行相关分析,比较海洛因成瘾组与正常对照组前额叶功能连接的变化情况.结果 以左侧前额叶为种子点进行功能连接分析,海洛因成瘾组左侧前额叶与左侧海马、右侧前扣带回、左侧额中回、右侧额中回、右侧楔前叶功能连接明显低于正常对照组:以右侧前额叶为种子点进行功能连接分析,海洛因成瘾组右侧前额叶与左侧眶额叶、左侧额中回功能连接明显低于正常对照组.结论 长期海洛因成瘾者前额叶与相关脑区的功能连接减弱,前额叶可能参与了海洛因成瘾的维持与戒断后复吸.

Abstract：

Objective To explore the changes of functional connectivity of the prefrontal cortex in chronic heroin addicts under resting-state functional MRI (fMRI). Methods Resting fMRI examination was performed on 13 chronic heroin addicts and 14 healthy volunteers. After pre-processing the resting-state fMRI data, the prefrontal cortex was selected as the seed region, with which a whole-brain voxel temporal correlation in Iow frequency fMRI fluctuations was analyzed and the changes of functional connectivity of the prefrontal lobe in both chronic heroin addicts and healthy volunteers were calculated with SPM5 software. Results Compared with that in the control group, the functional connectivity between the left prefrontal cortex and the left hippocampus, right anterior cingulate, left middle frontal gyrus, right middle frontal gyrus, right precuneus in the heroin addiction group was significantly decreased. The functional connectivity between the right prefrontal cortex and the left orbital frontal cortex, left middle frontal gyrus in thc heroin addiction group was also significantly decreased as compared with that in the control group. Conclusion Functional connectivity of prefrontal cortex in chronic heroin addicts decreases, indicating that the prefrontal cortex may be involved in the maintenance of heroin addiction and relapse after withdrawal.     

海洛因依赖稽延性戒断症状的多因素回归分析

目的探讨海洛因依赖稽延性戒断症状的影响因素。方法以一般人口学资料、汉密顿焦虑量表(HAMA)、稽延性戒断症状评定量表(PWSRS)、症状自评量表(SCL-90)、人格诊断问卷(PDQ)、药物成瘾者生命质量量表(QOL-DA)、社会支持评定量表(SSRS)为评估工具,评估120例海洛因依赖者稽延性戒断症状的心理、社会因素;并测定去甲肾上腺素(NE)、多巴胺(DA)、5-羟色胺(5-HT)浓度,进行动态心电图24小时心率变异分析(HRV),评估生物学因素。结果海洛因依赖稽延性戒断症状主要受复吸、SCL-90躯体化、PDQ回避型、动态心电图RR间期的标准差(SDNN)、动态心电图低频功率与高频功率之比(LF/HF)、5-HT的影响,标准回归系数依次为:0.241、0.388、0.109、0.213、0.183、0.077。结论海洛因依赖者稽延性戒断症状受生物、心理、社会三方面的影响,因此治疗需采取综合治疗措施。     

Drug addiction: Functional neurotoxicity of the brain reward systems

Drug addiction is a chronic relapsing brain disorder characterized by a compulsion to take a drug with loss of control over drug intake. The hypothesis under discussion here is that chronic drug use produces long-lasting dysfunctions in neurons associated with the brain reward circuitry, and this “functional neurotoxicity” of drugs of abuse leads to vulnerability to relapse and continued drug dependence. Several sources of reinforcement are associated with various components of the drug addiction cycle and much progress has been made in identifying the midbrain-basal forebrain neural elements involved in the positive reinforcing effects of drugs of abuse and more recently in the neural elements involved in the negative reinforcement associated with drug addiction. Key elements for the acute reinforcing effects of drugs of abuse include a macrostructure in the basal f orebrain called the extended amygdala that contains parts of the nucleus accumbens and amgydala and involves key neurotransmitters such as dopamine, opioid peptides, serotonin, GABA, and glutamate. Withdrawal from drugs of abuse is associated with subjective symptoms of negative affect and dysregu-lation of brain reward systems involving some of the same neurochemical systems implicated in the acute reinforcing effects of drugs of abuse. In addition, the functional toxicity of acute withdrawal is accompanied by recruitment of the brain stress neurotransmitter system corticotropin-releasing factor. During more prolonged abstinence, post-acute withdrawal, evidence is accumulating of continued dysregulation of the neural systems associated with drug reinforcement and stress regulation that may represent more subtle but persistent functional neurotoxic effects of chronic drug use and could be responsible for long-lasting vulnerability to relapse. Such functional neurotoxicity could be hypothesized to lead to a change in set point for drug reward that may represent an allostatic state contributing to vulnerability to relapse and re-entry into the addiction cycle. Elucidation of the specific neuropharmacological changes contributing to this prolonged functional neurotoxicity will be the challenge of future research on the neurobiology of drug addiction.