Alterations in the brain functional network of abstinent male individuals with methamphetamine use disorder.

Methamphetamine is a highly addictive psychostimulant drug that is abused globally and is a serious threat to health worldwide. Unfortunately, the specific mechanism underlying addiction remains unclear. Thus, this study aimed to investigate the characteristics of functional connectivity in the brain network and the factors influencing methamphetamine use disorder in patients using magnetic resonance imaging. We included 96 abstinent male participants with methamphetamine use disorder and 46 age- and sex-matched healthy controls for magnetic resonance imaging. Compared with healthy controls, participants with methamphetamine use disorder had greater impulsivity, fewer small-world attributes of the resting-state network, more nodal topological attributes in the cerebellum, greater functional connectivity strength within the cerebellum and between the cerebellum and brain, and decreased frontoparietal functional connectivity strength. In addition, after controlling for covariates, the partial correlation analysis showed that small-world properties were significantly associated with methamphetamine use frequency, psychological craving, and impulsivity. Furthermore, we revealed that the small-word attribute significantly mediated the effect of methamphetamine use frequency on motor impulsivity in the methamphetamine use disorder group. These findings may further improve our understanding of the neural mechanism of impulse control dysfunction underlying methamphetamine addiction and assist in exploring the neuropathological mechanism underlying methamphetamine use disorder-related dysfunction and rehabilitation.

Aberrant topology of white matter networks in patients with methamphetamine dependence and its application in support vector machine-based classification.

Brain white matter (WM) networks have been widely studied in neuropsychiatric disorders. However, few studies have evaluated alterations in WM network topological organization in patients with methamphetamine (MA) dependence. Therefore, using machine learning classification methods to analyze WM network topological attributes may give new insights into patients with MA dependence. In the study, diffusion tensor imaging-based probabilistic tractography was used to map the weighted WM networks in 46 MA-dependent patients and 46 control subjects. Using graph-theoretical analyses, the global and regional topological attributes of WM networks for both groups were calculated and compared to determine inter-group differences using a permutation-based general linear model. In addition, the study used a support vector machine (SVM) learning approach to construct a classifier for discriminating subjects with MA dependence from control subjects. Relative to the control group, the MA-dependent group exhibited abnormal topological organization, as evidenced by decreased small-worldness and modularity, and increased nodal efficiency in the right medial superior temporal gyrus, right pallidum, and right ventromedial putamen; the MA-dependent group had the higher hubness scores in 25 regions, which were mainly located in the default mode network. An SVM trained with topological attributes achieved classification accuracy, sensitivity, specificity, and kappa values of 98.09% ± 2.59%, 98.24% ± 4.00%, 97.94% ± 4.26%, and 96.18% ± 5.19% for patients with MA dependence. Our results may suggest altered global WM structural networks in MA-dependent patients. Furthermore, the abnormal WM network topological attributes may provide promising features for the construction of high-efficacy classification models.

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.

Changes in ALFF and ReHo values in methamphetamine abstinent individuals based on the Harvard-Oxford atlas: A longitudinal resting-state fMRI study.

Methamphetamine (MA) abuse has become a global public health problem due to damage to various systems throughout the body, especially the central nervous system. However, the differences in resting-state brain function between short-term and long-term abstinence, the pros and cons of treatments, and the relationship between resting-state brain function and behavioral tests are unknown. Sixty-three MA abstinent individuals were followed up for nearly 1 year and treated with three different methods. The amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) based on the Harvard-Oxford atlas (HOA) were measured by resting-state functional magnetic resonance imaging (fMRI). Impulsivity was evaluated by the Barratt Impulsivity Scale-11 (BIS-11). Brain regions with significant increases in ALFF and ReHo values in the long-term abstinent group compared to the short-term abstinent group were around the right frontal pole (McKetin et al., 2012, https://doi.org/10.1111/j.1360-0443.2012.03933.x) and right middle frontal gyrus (Wang et al., 2015, https://doi.org/10.1371/journal.pone.0133431). There were no significant differences among the three groups that experienced long-term abstinence. The changes in ALFF and ReHo in the right middle frontal gyrus were significantly associated with BIS total scores, BIS attention scores, and BIS nonplanning scores. The right middle frontal gyrus is a critical region in MA long-term abstinent individuals exposed to therapeutic intervention, and this region may be useful, when combined with BIS-11, as a potential biomarker to identify the effect of abstinence with therapeutic intervention in MA individuals.

Functional connectivity abnormalities underlying mood disturbances in male abstinent methamphetamine abusers.

Anxiety and depression are the most common withdrawal symptoms of methamphetamine (METH) abuse, which further exacerbate relapse of METH abuse. To date, no effective pharmacotherapy exists for METH abuse and its withdrawal symptoms. Therefore, understanding the neuromechanism underlying METH abuse and its withdrawal symptoms is essential for developing clinical strategies and improving patient care. The aims of this study were to investigate brain network abnormalities in METH abusers (MAs) and their associations with affective symptoms. Forty-eight male abstinent MAs and 48 age-gender matched healthy controls were recruited and underwent resting state functional magnetic resonance imaging (fMRI). The severity of patient anxiety and depressive symptoms were measured by Hamilton anxiety and depression rating scales, which decreased across the duration of abstinence. Independent component analysis was used to investigate the brain network functional connectivity (FC) properties. Compared with healthy controls, MAs demonstrated hypo-intra-network FC in the cerebellar network and hyper-intra-network FC in the posterior salience network. A whole-brain regression analysis revealed that FC strength of clusters located in the right rostral anterior cingulate cortex (rACC) within the ventromedial network (VMN) was associated with affective symptoms in the patients. Importantly, the intra-network FC strength of the rACC in VMN mediated the association between abstinence duration and the severity level of affective symptoms. Our results demonstrate alterations in brain functional networks underlying METH abuse, and that the FC of rACC within VMN serve as a neural substrate in the association between abstinence length and affective symptom severity in the MAs.

Brain dysfunction of methamphetamine-associated psychosis in resting state: Approaching schizophrenia and critical role of right superior temporal deficit.

Methamphetamine (MA)-associated psychosis (MAP) is highly debilitating and common among individuals who use the drug, yet the underlying neural mechanism is not clear. This study compared brain functions between patients with MAP and those with schizophrenia during resting state and investigated the effect of brain alteration on the association between MA use and psychosis in patients with MAP. Three groups, including 24 patients with MAP, 17 with schizophrenia in first-episode (SCZ) and 31 healthy controls (HCs), were included after receiving a resting-state functional MRI scan. The severity of psychosis was assessed with Positive and Negative Syndrome Scale (PANSS). Imaging data were analysed using regional homogeneity (ReHo) to measure individual's brain function. Compared with the HC subjects, the MAP and SCZ groups had significantly lower ReHo in the cortical regions including left postcentral cortex, right superior temporal gyrus and right rolandic operculum, while had higher ReHo in the left putamen, with brain dysfunctions being more pronounced in the SCZ group. Among the MAP subjects, a mediating effect of ReHo in the right superior temporal gyrus was found on the association between MA use frequency and PANSS positive score. MAP and schizophrenia had a common trend of brain alteration, with the dysfunction being more pronounced in schizophrenia. This finding implicated that MAP might be a condition with neuropathology approaching schizophrenia. The observed critical role of right superior temporal deficit between MA use and psychosis proposed a potential target for interventions.

It is never as good the second time around: Brain areas involved in salience processing habituate during repeated drug cue exposure in treatment engaged abstinent methamphetamine and opioid users.

The brain response to drug-related cues is an important marker in addiction-medicine. However, the temporal dynamics of this response in repeated exposure to cues are not well known. In an fMRI drug cue-reactivity task, the presence of rapid habituation or sensitization was investigated by modeling time and its interaction with condition (drug>neutral) using an initial discovery-sample. Replication of this temporal response was tested in two other clinical populations all abstinent during their early recovery (treatment). Sixty-five male participants (35.8 ± 8.4 years-old) with methamphetamine use disorder (MUD) were recruited as the discovery-sample from an abstinence-based residential treatment program. A linear mixed effects model was used to identify areas with a time-by-condition interaction in the discovery-sample. Replication of these effects was tested in two other samples (29 female with MUD from a different residential program and 22 male with opioid use disorder from the same residential program as the discovery sample). The second replication sample was re-tested within two weeks. In the discovery-sample, clusters within the VMPFC, amygdala and ventral striatum showed both a main effect of condition and a condition-by-time interaction, indicating a habituating response to drug-related but not neutral cues. The estimates for the main effects and interactions were generally consistent between the discovery and replication-samples across all clusters. The re-test data showed a consistent lack of drug > neutral and habituation response within all selected clusters in the second cue-exposure session. The VMPFC, amygdala and ventral striatum show habituation in response to drug-related cues which is consistent among different clinical populations. This habituated response in the first session of cue-exposure and lack of reactivity in the second session of exposure may be important for informing the development of cue-desensitization interventions.

Measurement of the adult human midbrain with transcranial ultrasound.

BACKGROUND: Transcranial sonography is increasingly used to aid clinical diagnoses of movement disorders, for example, to identify an enlarged area of substantia nigra echogenicity in patients with Parkinson's disease. OBJECTIVE: The current study investigated characteristics of the midbrain at the anatomical plane for quantification of substantia nigra echogenicity. METHODS: Area of substantia nigra echogenicity, cross-sectional area of the midbrain, and interpeduncular angle were quantified in two groups of adults aged 18-50 years: 47 healthy non-drug-using controls (control group) and 22 individuals with a history of methamphetamine use (methamphetamine group), a cohort with a high prevalence of enlarged substantia nigra echogenicity and thus risk of Parkinson's disease. RESULTS: In the control group, cross-sectional area of the midbrain (4.47±0.44 cm2) and interpeduncular angle were unaffected by age, sex, or image acquisition side. In the methamphetamine group, cross-sectional midbrain area (4.72±0.60 cm2) and area of substantia nigra echogenicity were enlarged compared to the control group, and the enlargement was sex-dependent (larger in males than females). Whole midbrain area and interpeduncular angle were found to be weak predictors of area of substantia nigra echogenicity after accounting for group and sex. CONCLUSIONS: History of methamphetamine use is associated with an enlarged midbrain and area of substantia nigra echogenicity, and the abnormality is more pronounced in males than females. Thus, males may be more susceptible to methamphetamine-induced changes to the brainstem, and risk of Parkinson's disease, than females.

Microglia imaging in methamphetamine use disorder: a positron emission tomography study with the 18 kDa translocator protein radioligand [F-18]FEPPA.

Activation of brain microglial cells, microgliosis, has been linked to methamphetamine (MA)-seeking behavior, suggesting that microglia could be a new therapeutic target for MA use disorder. Animal data show marked brain microglial activation following acute high-dose MA, but microglial status in human MA users is uncertain, with one positron emission tomography (PET) investigation reporting massively and globally increased translocator protein 18 kDa (TSPO; [C-11](R)-PK11195) binding, a biomarker for microgliosis, in MA users. Our aim was to measure binding of a second-generation TSPO radioligand, [F-18]FEPPA, in brain of human chronic MA users. Regional total volume of distribution (VT ) of [F-18]FEPPA was estimated with a two-tissue compartment model with arterial plasma input function for 10 regions of interest in 11 actively using MA users and 26 controls. A RM-ANOVA corrected for TSPO rs6971 polymorphism was employed to test significance. There was no main effect of group on [F-18]FEPPA VT (P = .81). No significant correlations between [F-18]FEPPA VT and MA use duration, weekly dosage, blood MA concentrations, regional brain volumes, and self-reported craving were observed. Our preliminary findings, consistent with our earlier postmortem data, do not suggest substantial brain microgliosis in MA use disorder but do not rule out microglia as a therapeutic target in MA addiction. Absence of increased [F-18]FEPPA TSPO binding might be related to insufficient MA dose or blunting of microglial response following repeated MA exposure, as suggested by some animal data.

Effects of chronic methamphetamine abuse on the retinal nerve fiber layer, ganglion cell layer and Bruch's membrane opening minimum rim width.

BACKGROUND: Methamphetamine (Meth) is a highly addictive and hallucinogenic agent which is used as the second most common illicit drug globally. Meth could affect the retina and optic nerve by inducing the release of vasoconstrictive agents such as endothelin 1 and induction of severe oxidative stress with accumulation of reactive oxygen species. AIM: To evaluate the effects of chronic Meth abuse on the retinal nerve fiber layer (RNFL), ganglion cell layer (GCL) and the Bruch's membrane opening minimum rim width (MRW). METHOD: In this case-control study, we recruited 55 Meth abusers and 49 healthy individuals with mean age of 44.63 ± 0.97 and 43.08 ± 0.91 years, respectively. RNFL thickness, GCL thickness and MRW were evaluated using optical coherence tomography. RESULTS: We found statistically significant decrease in RNFL, MRW thickness in Meth abusers (P: 0.002 and P: 0.006, respectively). We did not detect statistically significant difference regarding GCL thickness between the groups (P = 0.320). Our results showed a weak but statistically significant correlation of Meth dose increment and decrement of RNFL thickness ((P: 0.005, r = -0.193) and MRW (P: 0.013, r = -0.174). We found no correlation between duration of Meth consumption with RNFL and MRW thickness (P: 0.205, r= -0.124; P: 0.771, r= -0.029, respectively). CONCLUSION: We found a statistically significant adverse association in meth abusers with RNFL thickness and MRW. These two parameters were also statistically associated with the meth dose as measured by daily dose of Meth. Although we found a decrease in the GCL thickness, it did not reach statistical significance.

Higher impulsivity and lower grey matter volume in the bilateral prefrontal cortex in long-term abstinent individuals with severe methamphetamine use disorder.

BACKGROUND: Previous studies have shown that grey matter volume (GMV) might be lower in individuals with methamphetamine use disorder and that dynamic alterations in selected brain regions might appear in individuals after short-term abstinence. However, the GMV of brains in these individuals after long-term abstinence is poorly understood. Moreover, individuals with severe methamphetamine use disorder have been considered to have high levels of impulsivity, but the biological mechanism is still unclear. METHODS: In this study, the impulsivity of all participants was assessed using the Barratt Impulsiveness Scale (BIS-11). Using voxel-based morphometry (VBM) in conjunction with statistical parametric mapping on structural magnetic resonance images, the GMVs of the whole brain were compared among 32 drug-naïve healthy controls (HC) and 40 individuals with severe methamphetamine use disorder who had been abstinent for at least 20 months (SMUD-A). RESULTS: We observed significantly higher BIS-11 impulsivity scores and lower GMV in the bilateral superior frontal cortex of SMUD-A individuals than in those of control subjects. The impulsivity score was negatively correlated with GMV in the right superior frontal cortex. CONCLUSIONS: These findings offer novel evidence with respect to the impulsivity trait and brain GMV feature in long-term abstinent individuals with severe methamphetamine use disorder. Moreover, our findings suggest that lower GMV in the right superior frontal cortex might reflect a trait marker of higher impulsivity in this population.

Gray-matter structure in long-term abstinent methamphetamine users.

BACKGROUND: Previous studies of brain structure in methamphetamine users have yielded inconsistent findings, possibly reflecting small sample size and inconsistencies in duration of methamphetamine abstinence as well as sampling and analyses methods. Here we report on a relatively large sample of abstinent methamphetamine users at various stages of long-term abstinence. METHODS: Chronic methamphetamine users (n = 99), abstinent from the drug ranging from 12 to 621 days, and healthy controls (n = 86) received T1-weighted structural magnetic resonance imaging brain scans. Subcortical and cortical gray-matter volumes and cortical thickness were measured and the effects of group, duration of abstinence, duration of methamphetamine use and onset age of methamphetamine use were investigated using the Freesurfer software package. RESULTS: Methamphetamine users did not differ from controls in gray-matter volumes, except for a cluster in the right lateral occipital cortex where gray-matter volume was smaller, and for regions mainly in the bilateral superior frontal gyrui where thickness was greater. Duration of abstinence correlated positively with gray-matter volumes in whole brain, bilateral accumbens nuclei and insulae clusters, and right hippocampus; and with thickness in a right insula cluster. Duration of methamphetamine use correlated negatively with gray-matter volume and cortical thickness of a cluster in the right lingual and pericalcarine cortex. CONCLUSIONS: Chronic methamphetamine use induces hard-to-recover cortical thickening in bilateral superior frontal gyri and recoverable volumetric reduction in right hippocampus, bilateral accumbens nuclei and bilateral cortical regions around insulae. These alternations might contribute to methamphetamine-induced neurocognitive disfunctions and reflect a regional specific response of the brain to methamphetamine.

Methamphetamine and Opioid Cue Database (MOCD): Development and Validation.

INTRODUCTION: Drug cue reactivity (DCR) is widely used in experimental settings for both assessment and intervention. There is no validated database of pictorial cues available for methamphetamine and opioids. METHODS: 360 images in three-groups (methamphetamine, opioid and neutral (control)) matched for their content (objects, hands, faces and actions) were selected in an initial development phase. 28 participants with a history of both methamphetamine and opioid use (37.71 ± 8.11 years old, 12 female) with over six months of abstinence were asked to rate images for craving, valence, arousal, typicality and relatedness. RESULTS: All drug images were differentiated from neutral images. Drug related images received higher arousal and lower valence ratings compared to neutral images (craving (0-100) for neutral (11.5 ± 21.9), opioid (87.7 ± 18.5) and methamphetamine (88 ± 18), arousal (1-9) for neutral (2.4 ± 1.9), opioid (4.6 ± 2.7) and methamphetamine (4.6 ± 2.6), and valence (1-9) for neutral (4.8 ± 1.3), opioid (4.4 ± 1.9) and methamphetamine (4.4 ± 1.8)). There is no difference between methamphetamine and opioid images in craving, arousal and valence. There is a significant positive relationship between the amount of time that participants spent on drug-related images and the craving they reported for the image. Every 10 points of craving were associated with an increased response time of 383 ms. Three image sets were automatically selected for equivalent fMRI tasks (methamphetamine and opioids) from the database (tasks are available at github). CONCLUSION: The methamphetamine and opioid cue database (MOCD) provides a resource of validated images/tasks for future DCR studies. Additionally, researchers can select several sets of unique but equivalent images based-on their psychological/physical characteristics for multiple assessments/interventions.

Neurofunctional Differences Related to Methamphetamine and Sexual Cues in Men With Shorter and Longer Term Abstinence Methamphetamine Dependence.

BACKGROUND: Stimulant use and sexual behaviors have been linked in behavioral and epidemiological studies. Although methamphetamine-related neurofunctional differences have been investigated, few studies have examined neural responses to drug and sexual cues with respect to shorter or longer term methamphetamine abstinence in individuals with methamphetamine dependence. METHODS: Forty-nine men with shorter term methamphetamine abstinence, 50 men with longer term methamphetamine abstinence, and 47 non-drug-using healthy comparison men completed a functional magnetic resonance imaging cue-reactivity task consisting of methamphetamine, sexual, and neutral visual cues. RESULTS: Region-of-interest analyses revealed greater methamphetamine cue-related activation in shorter term methamphetamine abstinence and longer term methamphetamine abstinence individuals relative to healthy comparison men in the ventromedial prefrontal cortex. A significant interaction of group and condition in the anterior insula was found. Relative to healthy comparison participants, both shorter term methamphetamine abstinence and longer term methamphetamine abstinence groups displayed greater sexual cue-related anterior insula activation relative to methamphetamine cues and neutral cues, but there were no differences between shorter term methamphetamine abstinence and longer term methamphetamine abstinence groups in anterior insula responses. Subsequent whole-brain analyses indicated a group-by-condition interaction with longer term methamphetamine abstinence participants showing greater sexual-related activation in the left superior frontal cortex relative to healthy comparison men. Shorter term methamphetamine abstinence participants showed greater superior frontal cortex activation to sexual relative to neutral cues, and longer term methamphetamine abstinence participants showed greater superior frontal cortex activation to sexual relative to neutral and methamphetamine cues. CONCLUSIONS: The findings suggest that abstinence from methamphetamine may alter how individuals respond to drug and sexual cues and thus may influence drug use and sexual behaviors. Given the use of methamphetamine for sexual purposes and responses to natural vs drug rewards for addiction recovery, the findings may have particular clinical relevance.

Resting-state effective connectivity in the motive circuit of methamphetamine users: A case controlled fMRI study.

Methamphetamine (MA) and other psychostimulants target the motive circuit of the brain, which is involved in reward, behavioral sensitization, and relapse to drug-seeking/taking behavior. In spite of this fact, the data regarding the effective connectivity (EC) in this circuit among MA users is scarce. The present study aimed to assess resting-state EC in the motive circuit of MA users during abstinence using the fMRI technique. Seventeen MA users after abstinence and 18 normal controls were examined using a 3 T Siemens fMRI scanner. After extracting time series of the motive circuit, EC differences in the motive circuit were analyzed using dynamic causal modeling (DCM). The findings revealed that abstinent MA users had an enhanced EC from the prefrontal cortex (PFC) to the ventral palladium (VP) (PFC→VP) and on the mediodorsal thalamus (MD) self-loop (MD→MD), but they showed a decreased connectivity on the VP self-loop (VP→VP) compared to healthy controls. The findings suggest that abstinent MA users may suffer from a limited pathology in connectivity within the motive circuit involved in reward, behavioral sensitization, and relapse. The enhanced PFC→VP seems to be a compensatory mechanism to control or regulate the subcortical regions involved in reward and behavioral sensitization. Furthermore, the enhanced connectivity on the MD self-loop and the decreased connectivity on the VP self-loop in abstinent MA users may, at least partially, affect the output of the limbic system, which can be seen in the behavioral sensitization and relapse processes. Nonetheless, further investigation in this area is strongly recommended to elucidate the exact mechanisms involved.

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.

Regional differences in white matter integrity in stimulant use disorders: A meta-analysis of diffusion tensor imaging studies.

BACKGROUND: Converging lines of evidence from diffusion tensor imaging (DTI) studies reveal significant alterations in white matter (WM) microstructure in the prefrontal cortex of chronic stimulant users compared to controls, suggesting compromised axonal microstructure and/or myelin. METHODS: A meta-analysis of DTI-based WM integrity was conducted for white matter regions across the corpus callosum and association fibers. Articles were sourced and selected using PRISMA guidelines for systematic review and meta-analysis. Inclusion and exclusion criteria were determined by the authors in order to best capture WM integrity among individuals with primary stimulant use in comparison to healthy control subjects. RESULTS: Eleven studies that focused on region-of-interest (ROI)-based analysis of WM integrity were extracted from an initial pool of 113 independent studies. Analysis across ROIs indicated significantly lower fractional anisotropy (FA) values in stimulant use groups compared to controls with a small to moderate overall effect (Hedges' g = -0.37, 95% CI [-0.54, -0.20]). Eigenvalues were also analyzed, revealing a significant effect for radial diffusivity (RD; Hedges' g = 0.24, 95% CI [0.01, 0.47]) but not axial diffusivity (AD; Hedges' g = 0.05, 95% CI [-0.20, 0.29]) or mean diffusivity (MD; Hedges' g = 0.20, 95% CI [-0.01, 0.41]). Subgroup analyses based on specific ROIs, primary substance use, poly-substance use, and imaging technology were also explored. CONCLUSION: Results of the present study suggest a consistent effect of compromised WM integrity for individuals with stimulant use disorders. Furthermore, no significant differences were found between cocaine and methamphetamine-based groups.

Bayesian computational markers of relapse in methamphetamine dependence.

Methamphetamine use disorder is associated with a high likelihood of relapse. Identifying robust predictors of relapse that have explanatory power is critical to develop secondary prevention based on a mechanistic understanding of relapse. Computational approaches have the potential to identify such predictive markers of psychiatric illness, with the advantage of providing a finer mechanistic explanation of the cognitive processes underlying psychiatric vulnerability. In this study, sixty-two recently sober methamphetamine-dependent individuals were recruited from a 28-day inpatient treatment program, and completed a Stop Signal Task (SST) while undergoing functional magnetic resonance imaging (fMRI). These individuals were prospectively followed for 1 year and assessed for relapse to methamphetamine use. Thirty-three percent of followed participants reported relapse. We found that neural activity associated with two types of Bayesian prediction error, i.e. the difference between actual and expected need to stop on a given trial, significantly differentiated those individuals who remained abstinent and those who relapsed. Specifically, relapsed individuals exhibited smaller neural activations to such Bayesian prediction errors relative to those individuals who remained abstinent in the left temporoparietal junction (Cohen's d = 0.91), the left inferior frontal gyrus (Cohen's d = 0.57), and left anterior insula (Cohen's d = 0.63). In contrast, abstinent and relapsed participants did not differ in neural activation to non-model based task contrasts or on various self-report clinical measures. In conclusion, Bayesian cognitive models may help identify predictive biomarkers of relapse, while providing a computational explanation of belief processing and updating deficits in individuals with methamphetamine use disorder.

Support vector machine-based multivariate pattern classification of methamphetamine dependence using arterial spin labeling.

Arterial spin labeling (ASL) magnetic resonance imaging has been widely applied to identify cerebral blood flow (CBF) abnormalities in a number of brain disorders. To evaluate its significance in detecting methamphetamine (MA) dependence, this study used a multivariate pattern classification algorithm, ie, a support vector machine (SVM), to construct classifiers for discriminating MA-dependent subjects from normal controls. Forty-five MA-dependent subjects, 45 normal controls, and 36 heroin-dependent subjects were enrolled. Classifiers trained with ASL-CBF data from the left or right cerebrum showed significant hemispheric asymmetry in their cross-validated prediction performance (P < 0.001 for accuracy, sensitivity, specificity, kappa, and area under the curve [AUC] of the receiver operating characteristics [ROC] curve). A classifier trained with ASL-CBF data from all cerebral regions (bilateral hemispheres and corpus callosum) was able to differentiate MA-dependent subjects from normal controls with a cross-validated prediction accuracy, sensitivity, specificity, kappa, and AUC of 89%, 94%, 84%, 0.78, and 0.95, respectively. The discrimination map extracted from this classifier covered multiple brain circuits that either constitute a network related to drug abuse and addiction or could be impaired in MA-dependence. The cerebral regions contribute most to classification include occipital lobe, insular cortex, postcentral gyrus, corpus callosum, and inferior frontal cortex. This classifier was also specific to MA-dependence rather than substance use disorders in general (ie, 55.56% accuracy for heroin dependence). These results support the future utilization of ASL with an SVM-based classifier for the diagnosis of MA-dependence and could help improve the understanding of MA-related neuropathology.