Difference in topological organization of white matter structural connectome between methamphetamine and heroin use disorder.

The psychological symptoms caused by heroin and methamphetamine are significantly different in people with substance use disorders. The topological organization of structural connections that may underlie these differences remains unknown. The study sample consisted of 23 males with methamphetamine use disorder (MAUD), 20 males with heroin use disorder (HUD), and 21 male healthy controls (HCs) who were demographically matched. Diffusion tensor imaging and probabilistic tractography were used for white matter network construction. Psychological symptoms were evaluated by the Symptom Checklist-90. Using graph theoretical analysis, we examined the difference in graph-level and nodal-level properties among the groups. The network Hubs distribution and the relationship between the network alterations and psychological symptoms were identified. The MAUD group demonstrated significantly higher scores on anxiety, hostility, and symptoms of schizophrenia than the HUD and HCs groups. The HUD group showed significantly higher global efficiency and network strength than the HCs group, and higher network strength than the MAUD group. Compared with the HUD group, the MAUD group showed significantly lower Nodal Strength and efficiency, distributed mainly in the temporal, parietal, and occipital regions. We also found the network Hubs were decreased in the MAUD group, but increased in the HUD group. The Nodal Strength in the right superior temporal gyrus was significantly correlated with psychological symptoms in the MAUD group. These findings reflect the significant differences in topological structural connection between HUD and MAUD. This evidence helps shed some light on the neurobiological mechanisms of the psychological differences between HUD and MAUD, and extend our understanding of the structural disruption underlying MAUD-related psychological symptoms.

Bouncing back: Brain rehabilitation amid opioid and stimulant epidemics.

Recent methamphetamine and opioid use epidemics are a major public health concern. Chronic stimulant and opioid use are characterized by significant psychosocial, physical and mental health costs, repeated relapse, and heightened risk of early death. Neuroimaging research highlights deficits in brain processes and circuitry that are linked to responsivity to drug cues over natural rewards as well as suboptimal goal-directed decision-making. Despite the need for interventions, little is known about (1) how the brain changes with prolonged abstinence or as a function of various treatments; and (2) how symptoms change as a result of neuromodulation. This review focuses on the question: What do we know about changes in brain function during recovery from opioids and stimulants such as methamphetamine and cocaine? We provide a detailed overview and critique of published research employing a wide array of neuroimaging methods - functional and structural magnetic resonance imaging, electroencephalography, event-related potentials, diffusion tensor imaging, and multiple brain stimulation technologies along with neurofeedback - to track or induce changes in drug craving, abstinence, and treatment success in stimulant and opioid users. Despite the surge of methamphetamine and opioid use in recent years, most of the research on neuroimaging techniques for recovery focuses on cocaine use. This review highlights two main findings: (1) interventions can lead to improvements in brain function, particularly in frontal regions implicated in goal-directed behavior and cognitive control, paired with reduced drug urges/craving; and (2) the targeting of striatal mechanisms implicated in drug reward may not be as cost-effective as prefrontal mechanisms, given that deep brain stimulation methods require surgery and months of intervention to produce effects. Overall, more studies are needed to replicate and confirm findings, particularly for individuals with opioid and methamphetamine use disorders.

Mega-Analysis of Gray Matter Volume in Substance Dependence: General and Substance-Specific Regional Effects.

OBJECTIVE: Although lower brain volume has been routinely observed in individuals with substance dependence compared with nondependent control subjects, the brain regions exhibiting lower volume have not been consistent across studies. In addition, it is not clear whether a common set of regions are involved in substance dependence regardless of the substance used or whether some brain volume effects are substance specific. Resolution of these issues may contribute to the identification of clinically relevant imaging biomarkers. Using pooled data from 14 countries, the authors sought to identify general and substance-specific associations between dependence and regional brain volumes. METHOD: Brain structure was examined in a mega-analysis of previously published data pooled from 23 laboratories, including 3,240 individuals, 2,140 of whom had substance dependence on one of five substances: alcohol, nicotine, cocaine, methamphetamine, or cannabis. Subcortical volume and cortical thickness in regions defined by FreeSurfer were compared with nondependent control subjects when all sampled substance categories were combined, as well as separately, while controlling for age, sex, imaging site, and total intracranial volume. Because of extensive associations with alcohol dependence, a secondary contrast was also performed for dependence on all substances except alcohol. An optimized split-half strategy was used to assess the reliability of the findings. RESULTS: Lower volume or thickness was observed in many brain regions in individuals with substance dependence. The greatest effects were associated with alcohol use disorder. A set of affected regions related to dependence in general, regardless of the substance, included the insula and the medial orbitofrontal cortex. Furthermore, a support vector machine multivariate classification of regional brain volumes successfully classified individuals with substance dependence on alcohol or nicotine relative to nondependent control subjects. CONCLUSIONS: The results indicate that dependence on a range of different substances shares a common neural substrate and that differential patterns of regional volume could serve as useful biomarkers of dependence on alcohol and nicotine.

[Change of brain structure imaging of long-term withdrawal of methamphetamine-dependent patients].

OBJECTIVE: To explore the characteristics of brain structure in patients with long-term withdrawal of methamphetamine-dependence.
 Methods: A total of 44 patients with withdrawal of methamphetamine-dependent for more than 14 months were recruited, who met the diagnostic criteria for substance dependence in the fifth edition of the American Mental Disorders Diagnostic and Statistical Manual (DSM-V), and 40 healthy subjects were used as the control. In addition to the general scale of drug-relevant survey, the subjects received the 3.0T magnetic resonance high-resolution scan. The voxel-based morphometric measurements for the subject's brain gray volume were conducted.
 Results: There was no significant difference in age, education, smoking and alcohol consumption between the methamphetamine-dependent withdrawal group and the control group (P>0.05). The volumes for the bilateral cerebellum, the left side of temporal gyrus and the right side of the lingual gyrus in the methamphetamine-dependent withdrawal group were increased than those in the control group. The volumes for the bilateral lingual gyrus and bilateral cuneus in the methamphetamine-dependent withdrawal group were decreased than those in the control group. The volumes of left of cuneus and cerebellum were positively correlated with the duration of abstinence.
 Conclusion: After long-term abstinence, although the patients still show abnormal brain structure, their behavior and cognitive function is improved. The cerebral nerve structural is recovered from long-term abstinence.

Neuroimaging Impaired Response Inhibition and Salience Attribution in Human Drug Addiction: A Systematic Review.

The impaired response inhibition and salience attribution (iRISA) model proposes that impaired response inhibition and salience attribution underlie drug seeking and taking. To update this model, we systematically reviewed 105 task-related neuroimaging studies (n > 15/group) published since 2010. Results demonstrate specific impairments within six large-scale brain networks (reward, habit, salience, executive, memory, and self-directed networks) during drug cue exposure, decision making, inhibitory control, and social-emotional processing. Addicted individuals demonstrated increased recruitment of these networks during drug-related processing but a blunted response during non-drug-related processing, with the same networks also being implicated during resting state. Associations with real-life drug use, relapse, therapeutic interventions, and the relevance to initiation of drug use during adolescence support the clinical relevance of the results. Whereas the salience and executive networks showed impairments throughout the addiction cycle, the reward network was dysregulated at later stages of abuse. Effects were similar in alcohol, cannabis, and stimulant addiction.

Structural abnormality of substantia nigra induced by methamphetamine abuse.

BACKGROUND: Methamphetamine abuse has been linked to an increased risk of Parkinson's disease. OBJECTIVE: The objective of this study was to investigate structural abnormality of the substantia nigra in past methamphetamine users using transcranial sonography. METHODS: In a cross-sectional, observational study, echogenicity of the substantia nigra was assessed in 59 past methamphetamine users and 59 matched controls. The frequencies of an abnormal spatial extension of the substantia nigra as well as the average sizes of left and right substantia nigra were evaluated. RESULTS: The average echogenic size of the substantia nigra was larger in methamphetamine users (0.22 ± 0.06 cm2 ) when compared with controls (0.17 ± 0.05 cm2 , P < .001). Furthermore, the frequency of enlarged, echogenic substantia nigra was increased in methamphetamine users (42% vs 12% in controls, P < .001). Partial correlation analysis revealed an association of echogenic substantia nigra size with estimated total lifetime intake of methamphetamine (r55 = 0.395, P = .002). CONCLUSIONS: Current data link methamphetamine abuse in humans to injury of substantia nigra neurons and an increased risk of Parkinson's disease. © 2017 International Parkinson and Movement Disorder Society.

Is an Abnormal ECG Just the Tip of the ICE-berg? Examining the Utility of Electrocardiography in Detecting Methamphetamine-Induced Cardiac Pathology.

BACKGROUND: Methamphetamine use is escalating in Australia and New Zealand, with increasing emergency department attendance and mortality. Cardiac complications play a large role in methamphetamine-related mortality, and it would be informative to assess the frequency of abnormal electrocardiograms (ECGs) amongst methamphetamine users. OBJECTIVE: To determine the frequency and severity of ECG abnormalities amongst methamphetamine users compared to a control group. METHODS: We conducted a retrospective cohort analysis on 212 patients admitted to a tertiary hospital (106 patients with methamphetamine use, 106 age and gender-matched control patients). Electrocardiograms were analysed according to American College of Cardiology guidelines. RESULTS: Mean age was 33.4 years, with 73.6% male gender, with no significant differences between groups in smoking status, ECG indication, or coronary angiography rates. Methamphetamine users were more likely to have psychiatric admissions (22.6% vs 1.9%, p<0.0001). Overall, ECG abnormalities were significantly more common (71.7% vs 32.1%, p<0.0001) in methamphetamine users, particularly tachyarrhythmias (38.7% vs 26.4%, p<0.0001), right axis deviation (7.5% vs 0.0%, p=0.004), left ventricular hypertrophy (26.4% vs 4.7%, p<0.0001), P pulmonale pattern (7.5% vs 0.9%, p=0.017), inferior Q waves (10.4% vs 0.0%, p=0.001), lateral T wave inversion (3.8% vs 0.0%, p=0.043), and longer QTc interval (436.41±31.61ms vs 407.28±24.38ms, p<0.0001). Transthoracic echocardiogram (n=24) demonstrated left ventricular dysfunction (38%), thrombus (8%), valvular lesions (17%), infective endocarditis (17%), and pulmonary hypertension (13%). Electrocardiograms were only moderately sensitive at predicting abnormal TTE. CONCLUSION: Electrocardiographic abnormalities are more common in methamphetamine users than age and gender-matched controls. Due to the high frequency of abnormalities, ECGs should be performed in all methamphetamine users who present to hospital. Methamphetamine users with abnormal ECGs should undergo further cardiac investigations.

Decreased subcortical volumes in alcohol dependent individuals: effect of polysubstance use disorder.

Chronic alcohol use has widespread effects on brain morphometry. Alcohol dependent individuals are often diagnosed with comorbid substance use disorders. Alterations in brain morphometry may be different in individuals that are dependent on alcohol alone and individuals dependent on alcohol and other substances. We examined subcortical brain volumes in 37 individuals with alcohol dependence only (ADO), 37 individuals with polysubstance use disorder (PS) and 37 healthy control participants (HC). Participants underwent a structural MR scan and a model-based segmentation tool was used to measure the volume of 14 subcortical regions (bilateral thalamus, caudate, putamen, globus pallidus, hippocampus, amygdala and nucleus accumbens). Compared to HC, ADO had smaller volume in the bilateral hippocampus, right nucleus accumbens and right thalamus. PS only had volume reductions in the bilateral thalamus compared to HC. PS had a larger right caudate compared to ADO. Subcortical volume was negatively associated with drinking measures only in the ADO group. This study confirms the association between alcohol dependence and reductions in subcortical brain volume. It also suggests that polysubstance use interacts with alcohol use to produce limited subcortical volume reduction and at least one region of subcortical volume increase. These findings indicate that additional substance use may mask damage through inflammation or may function in a protective manner, shielding subcortical regions from alcohol-induced damage.

Methamphetamine causes microglial activation in the brains of human abusers.

Methamphetamine is a popular addictive drug whose use is associated with multiple neuropsychiatric adverse events and toxic to the dopaminergic and serotonergic systems of the brain. Methamphetamine-induced neuropathology is associated with increased expression of microglial cells that are thought to participate in either pro-toxic or protective mechanisms in the brain. Although reactive microgliosis has been observed in animal models of methamphetamine neurotoxicity, no study has reported on the status of microglial activation in human methamphetamine abusers. The present study reports on 12 abstinent methamphetamine abusers and 12 age-, gender-, and education-matched control subjects who underwent positron emission tomography using a radiotracer for activated microglia, [(11)C](R)-(1-[2-chlorophenyl]-N-methyl-N-[1-methylpropyl]-3-isoquinoline carboxamide) ([(11)C](R)-PK11195). Compartment analysis was used to estimate quantitative levels of binding potentials of [(11)C](R)-PK11195 in brain regions with dopaminergic and/or serotonergic innervation. The mean levels of [(11)C](R)-PK11195 binding were higher in methamphetamine abusers than those in control subjects in all brain regions (>250% higher; p < 0.01 for all). In addition, the binding levels in the midbrain, striatum, thalamus, and orbitofrontal and insular cortices (p < 0.05) correlated inversely with the duration of methamphetamine abstinence. These results suggest that chronic self-administration of methamphetamine can cause reactive microgliosis in the brains of human methamphetamine abusers, a level of activation that appears to subside over longer periods of abstinence.