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Voxel-based morphometry has been used to explore gray matter alterations in cocaine and methamphetamine dependence. However, the results of this research are inconsistent.
The current study meta-analytically examined neuroimaging findings of all studies published before 2014 using the Anisotropic Effect-Size Signed Differential Mapping (ES-SDM).
In...
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Context 1
... ES-SDM meta-analysis identified five regions of significant gray matter reduction in cocaine-dependent indi- viduals as compared to healthy controls ( Figure 1, Table 3). Specifically, peak reductions were observed in the right insula and surrounding regions, left inferior temporal gyrus, right Rolandic operculum (including the Heschl gyrus), and two coordinates unidentified by ES-SDM, consisting of multiple regions. ...
Context 2
... Voxel-based ES-SDM meta-analysis identified three regions of significant gray matter reduction in metham- phetamine dependent individuals as compared to healthy controls ( Figure 2, Table 4). Peak reductions were observed in the bilateral insular cortices (with larger cluster in the left) and the right inferior parietal gyrus Cluster breakdown revealed reductions in the bilateral superior temporal gyri, striatal regions, and the bilateral inferior frontal gyrus (see Table 3). There were no increases in regional gray matter. ...
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Rationale
Stimulant use is a significant and prevalent problem, particularly in criminal populations. Previous studies found that cocaine and methamphetamine use is related to impairment in identifying emotions and empathy. Stimulant users also have abnormal neural structure and function of the ventromedial prefrontal cortex (vmPFC), amygdala, and...
Citations
... Some studies had already identified alterations in the right inferior and middle temporal cortex among cocaine users, yet without comparing routes of cocaine use (Ide et al., 2014;Moreno-López et al., 2012). A meta-analysis, which reviewed original studies exploring anatomical MRI in cocaine and methamphetamine-dependent patients, reported that lower GM volumes in the right inferior and middle temporal gyri were associated with longer cocaine use in cocaine-dependent patients (Hall et al., 2015). Among studies exploring brain alterations in crack-cocaine users compared to healthy controls, one study comparing nine homeless crack-cocaine dependent users to healthy controls reported alterations in the temporal cortex, showing reduced volumes of the right superior temporal gyrus (RosalynE et al., 2011). ...
... The higher frequency of neuropsychiatric complications observed in female patients is thought to be secondary to METH-mediated changes in brain functions and structures (Du et al., 2015;Hall et al., 2015;Kogachi, Chang, Alicata, Cunningham, & Ernst, 2017). As described below, METH-induced changes in brain structures are sex-dependent. ...
Methamphetamine (METH) is the most commonly misused amphetamine-type stimulant throughout the globe. METH is very rewarding, and its misuse can lead to a diagnosis of METH use disorder (MUD). Although METH use is observed in both sexes, there are, however, reported differences in the clinical manifestations of METH use and its consequences. These observations indicate the need for more research on the long-term sex-dependent consequences of METH taking in both preclinical and clinical settings. In effect, sex is a biological variable that can impact conclusions drawn from various basic and clinical studies. Thus, the present chapter provides a succinct review of the current state of the research on METH and its sex-associated consequences. In addition to behavioral and cognitive aspects of METH use, we discuss METH-induced changes in neurotransmitter systems and structures in the brain. Thus, the book chapter serves to highlight the significance of sex as a critical element that needs to be considered during discussions of novel therapeutic approaches to MUD.
... The AUD group had significantly different DC and FC values in the PreCG and the IPL. The PreCG region is known as the primary motor center of the brain [18], involved in the integration of information related to the sensory, motor, attention, and reward circuits [19][20][21][22]. Our findings of reduced DC and FC in the left PreCG region of AUD patients further enriched the evidence that chronic alcohol consumption might cause functional changes in the PreCG, which would affect sensory, motor and attention functions as well as brain reward mechanisms. ...
Background
Alcohol use disorder (AUD) has a negative impact on one’s health and wastes a lot of societal resources since it damages one’s brain tissue. Yet the knowledge of the neural mechanisms underlying alcohol addiction still remains limited. This study aims to investigate the neural mechanisms underlying alcohol addiction by using voxel-wise binarized degree centrality (DC), weighted DC and functional connectivity (FC) methods to analyze brain network activity in individuals with AUD.
Methods
Thirty-three AUD patients and 29 healthy controls (HC) participated in this study. Binarized and weighted DC approach coupled with a second seed-based FC algorithm was used to assess the abnormal intrinsic hub features in AUD. We also examined the correlation between changes in functional network nodes and the severity of alcohol dependence.
Results
Thirty AUD patients and 26 HC were retained after head motion correction. The spatial distribution maps of the binarized DC and weighted DC for the AUD and HC groups were roughly similar. In comparison to HC, the AUD group had decreased binarized DC and decreased weighted DC in the left precentral gyrus (PreCG) and the left inferior parietal lobule (IPL). Significantly different brain regions in the DC analysis were defined as seed points in the FC analysis. Compared with HC, changes in FC within the right inferior temporal gyrus (ITG), right middle temporal gyrus (MTG), left dorsolateral superior frontal gyrus (SFGdor), bilateral IPL, left precuneus (PCUN), left lingual gyrus (LING), right cerebellum_crus1/ITG/inferior occipital gyrus (IOG) and right superior parietal gyrus (SPG) were observed. The correlation analysis revealed that FC of right MTG-right PreCG was negatively correlated with MAST scores, and FC of right IPL-left IPL was positively correlated with ADS scores.
Conclusions
Alcohol use disorder is associated with aberrant regional activities in multiple brain areas. Binarized DC, weighted DC and FC analyses may be useful biological indicators for the detection of regional brain activities in patients with AUD. Intergroup differences in FC have also been observed in AUD patients, and these variations were connected to the severity of the symptoms. The AUD patients with lower FC value of the right IPL - left IPL has a lighter dependence on alcohol. This difference in symptom severity may be a compensation for cognitive impairment, indicating a difference in pathological pathways. Future AUD research will now have a fresh path thanks to these discoveries.
... Monterosso et al.(Monterosso et al. 2005) showed reduced GMV in the parsopercularis in MA abusers. A meta-analysis of neuroimaging studies of cocaine and MA dependence observed a decrease in GMV in the left precentral(Hall et al. 2015). Interestingly, a study comparing the differences in cortical and subcortical GMV and cortical thickness between 99 long-term abstinent MUDs and 86 HCs found thickened cortices bilaterally on the frontal surface in MUDs, which the authors suggested was related to glial cell proliferation induced by long-term MA use(Nie et al. 2020). ...
Background
Methamphetamine (MA) is widely abused worldwide, but the brain imaging mechanisms underlying its cognitive function are unclear. This study aimed to explore the cognitive function characteristics of individuals with MA use disorders (MUDs) and their relationship with structural brain images from a multidimensional perspective.
Methods
45 MUDs and 43 health control (HCs) were included in this study. The MATRICS Consensus Cognitive Battery was performed to assess the cognitive function among the subjects, and a 3.0T magnetic resonance imaging scanner was utilized for structural data acquisition.
Results
Compared with the HC group, the MUD group had small gray matter volume in the left middle frontal, right insula, left postcentral, and bilateral angular gyrus, while the left superior frontal, left precentral, left postcentral, left supramarginal, left parstriangularis, and left parsopercularis had thin cortical thickness (PFDR-corr < 0.05, cluster > 100). The digit-symbol coding test (DSCT) regression model demonstrated a significant interaction of the group with the cortical thickness of the left parsopercularis (p = 0.04) and left precentral (p = 0.01). For neuropsychology assessment battery-mazes (NAB-Mazes), cortical thickness of the left parsopercularis was positively correlated with NAB-Mazes scores (p = 0.02), and the group interaction was significant (p = 0.001). For the continuous performance test (CPT), cortical thickness of the left superior frontal was negatively correlated with CPT scores (p = 0.03).
Conclusion
MUDs exhibit altered gray matter morphology in several brain regions, where alterations in frontal cortex thickness may underlie the neuroanatomy of cognitive deficits common to MUDs.
... Chronic cocaine use has been consistently associated with a range of structural brain alterations, including volumetric changes in cortical and subcortical regions and disruption of white matter tracts [1][2][3][4][5]. Although some recent longitudinal studies have suggested that neuroanatomical alterations in fronto-cortical areas covary with changes of cocaine consumption [6,7], most of the findings are limited to cross-sectional observations. ...
... Finally, we evaluated longitudinal changes in NfL levels in relation to objectively confirmed changes in cocaine consumption across a 4-month follow-up period as determined by hair testing. Based on previous crosssectional findings linking structural brain alterations with chronic cocaine use [1][2][3][4], we hypothesized that NfL levels would be elevated in CU at baseline in a dose-dependent manner. Moreover, we expected that NfL levels at follow-up would be associated with changes in cocaine consumption during the 4-month interval, as previously shown for anatomical and cognitive measures in cocaine user populations [7,22,23]. ...
... Postmortem investigations also suggested damage to dopaminergic neurons in the basal ganglia and white matter disruption in CU [4,48]. Neuroimaging studies have found reductions in gray matter volumes, especially in the frontal and insular areas [1,3,5], and widespread alterations of major white matter tracts in CU [4]. These structural changes were linked to cognitive dysfunctions and seemed to be partially reversible after longer periods of abstinence or decreased cocaine use [2,7]. ...
The identification of a blood marker of brain pathology that is sensitive to substance-induced neurotoxicity and dynamically responds to longitudinal changes in substance intake would substantially improve clinical monitoring in the field of substance use and addiction. Here, we explored the hypothesis that plasma levels of neurofilament light chain (NfL), a promising marker of neuroaxonal pathology, are elevated in chronic cocaine users and longitudinally associated with changes in cocaine use. Plasma NfL levels were determined using single molecule array (SIMOA) technology at baseline and at a 4-month follow-up. Substance use was subjectively assessed with an extensive interview and objectively measured via toxicological analysis of urine and 4-month hair samples. In a generalized linear model corrected for sex, age, and body mass index, NfL plasma levels were elevated in cocaine users (n=35) compared to stimulant-naïve healthy controls (n=35). A positive correlation between cocaine hair concentration and NfL levels was also found. Changes in cocaine hair concentration (group analysis of increasers vs. decreasers) over the 4-month interval predicted NfL levels at follow-up, indicating a rise in NfL with increased cocaine use and a reduction with decreased use. No associations between use or change of use of other substances (including the neurotoxic cocaine adulterant levamisole) and NfL levels were found. Our findings demonstrate that NfL is a sensitive marker for assessing cocaine-related neuroaxonal pathology, supporting the utility of blood NfL analysis in addiction research but also suggesting the detailed assessment of substance use in neurological studies and diagnostics.
... 5 Interestingly, GM alterations show a relationship with the characteristics of substance use. Indeed, the duration of drug intake has been associated with abnormal GM volume in the right insula, the right gyrus rectus, the bilateral middle temporal gyrus and the right inferior frontal gyrus, 6 whereas trait and behavioural impulsivity have been associated with the reduction of GM volume in fronto-parietal areas in cocaine users. 7 Although brain volume is related to surfaced-base measures, these latter indexes may be more sensitive to cortical reductions, as shown in several neuropsychiatry disorders and aging. ...
Cocaine use is a worldwide health problem with psychiatric, somatic and socioeconomic complications, being the second most widely used illicit drug in the world. Despite several structural neuroimaging studies, the alterations in cortical morphology associated with cocaine use and addiction are still poorly understood. In this study, we compared the complexity of cortical folding (CCF), a measure that aims to summarize the convoluted structure of the cortex between patients with cocaine addiction (n = 52) and controls (n = 36), and correlated it with characteristics of addiction and impulsivity. We found that patients with cocaine addiction had greater impulsivity and showed reduced CCF in a cluster that encompassed the left insula and the supramarginal gyrus (SMG) and in one in the left medial orbitofrontal cortex. Finally, the CCF in the left medial orbitofrontal cortex was correlated with the age of onset of cocaine addiction and with attentional impulsivity. Overall, our findings suggest that chronic cocaine use is associated with changes in the cortical surface in the fronto‐parieto‐limbic regions that underlie emotional regulation and these changes are associated with earlier cocaine use. Future longitudinal studies are warranted to unravel the association of these changes with the diathesis for the disorder and with the chronic use of this substance. Chronic cocaine use is reduced with altered complexity of cortical folding in the insula and in the orbitofrontal cortex. Reduced cortical complexity correlated with the severity of the addiction and with impulsivity. Cortical complexity changes may be associated with the risk of developing addiction as well as the reinforcement of the use of the substance itself.
... Drug addiction is often accompanied by cognitive impairment. Many clinical studies have indicated significant reductions in the gray matter of the temporal, frontal, and parietal cortices in METH abusers (Hall et al. 2015). The common cognitive impairment phenomena associated with chronic METH intake are manifested as decreases in situational memory, executive function, language skills, visual construction skills, and information processing speed as well as lasting impairments in learning, memory, and executive function (Recinto et al. 2012;Scofield et al. 2015). ...
Methamphetamine (METH) is an amphetamine-type stimulant that is highly toxic to the central nervous system (CNS). Repeated intake of METH can lead to addiction, which has become a globalized problem, resulting in multiple public health and safety problems. Recently, the non-coding RNA (ncRNA) has been certified to play an essential role in METH addiction through various mechanisms. Herein, we mainly focused on three kinds of ncRNAs including long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs), which are involved in neurotoxicity effects such as cognitive impairment, behavioral abnormalities, and psychiatric disorders due to METH abuse. In addition, differential expression (DE) ncRNAs also suggest that specific responses and sensitivity to METH neurotoxicity exist in different brain regions and cells. We summarized the relationships between the ncRNAs and METH-induced neurotoxicity and psychiatric disturbances, respectively, hoping to provide new perspectives and strategies for the prevention and treatment of METH abuse.
Graphical Abstract
Schematic diagram of the non-coding RNAs (ncRNAs) was involved in methamphetamine (METH)-induced neurotoxicity. The ncRNAs were involved in METH-induced blood–brain barrier disruption, neuronal, astrocyte, and microglial damage, and synaptic neurotransmission impairment. The study of ncRNAs is a hot spot in the future to further understand the neurotoxicity of METH and provide more favorable scientific support for clinical diagnosis and innovation of related treatments.
... The insular cortex is known to be involved in interoception, decision making, anxiety, pain perception, cognition, mood, threat recognition, and conscious urges (Ibrahim et al., 2019). In MA users, the left insula has been reported to present volume reduction (Hall et al., 2015), greater activation across risky and safe decisions (Gowin et al., 2014), and decreased glucose metabolism (Vuletic et al., 2018). Consistent with these findings, our results, i.e., the left insula as the only structure with MArelated increment of betweenness centrality and as important features for constructing a high-efficacy classifier, supports the perspective that left insular cortex is involved in key aspects underlying MA-dependence. ...
Brain resting-state functional connectivity (rsFC) has been widely analyzed in substance use disorders (SUDs), including methamphetamine (MA) dependence. Most of these studies utilized Pearson correlation analysis to assess rsFC, which cannot determine whether two brain regions are connected by direct or indirect pathways. Moreover, few studies have reported the application of rsFC-based graph theory in MA dependence. We evaluated alterations in Tikhonov regularization-based rsFC and rsFC-based topological attributes in 46 MA-dependent patients, as well as the correlations between topological attributes and clinical variables. Moreover, the topological attributes selected by least absolute shrinkage and selection operator (LASSO) were used to construct a support vector machine (SVM)-based classifier for MA dependence. The MA group presented a subnetwork with increased rsFC, indicating overactivation of the reward circuit that makes patients very sensitive to drug-related visual cues, and a subnetwork with decreased rsFC suggesting aberrant synchronized spontaneous activity in subregions within the orbitofrontal cortex (OFC) system. The MA group demonstrated a significantly decreased area under the curve (AUC) for the clustering coefficient (Cp) (Pperm < 0.001), shortest path length (Lp) (Pperm = 0.007), modularity (Pperm = 0.006), and small-worldness (σ, Pperm = 0.004), as well as an increased AUC for global efficiency (E.glob) (Pperm = 0.009), network strength (Sp) (Pperm = 0.009), and small-worldness (ω, Pperm < 0.001), implying a shift toward random networks. MA-related increased nodal efficiency (E.nodal) and altered betweenness centrality were also discovered in several brain regions. The AUC for ω was significantly positively associated with psychiatric symptoms. An SVM classifier trained by 36 features selected by LASSO from all topological attributes achieved excellent performance, cross-validated prediction area under the receiver operating characteristics curve, accuracy, sensitivity, specificity, and kappa of 99.03 ± 1.79, 94.00 ± 5.78, 93.46 ± 8.82, 94.52 ± 8.11, and 87.99 ± 11.57%, respectively (Pperm < 0.001), indicating that rsFC-based topological attributes can provide promising features for constructing a high-efficacy classifier for MA dependence.
... While two very small clusters in the right superior frontal gyrus reached significance when compared to the healthy controls in post-hoc analyses after the ANOVA, these significances were not replicated in the validating VBM analysis with FSL-Palm. MA users had often been reported to have reduced cortical volumes than did control individuals (Hall et al., 2015) (London et al., 2015). However, multiple of the studies did not excluded patients with MA-associated psychosis from MA users without psychosis (London et al., 2015). ...
Background and Hypothesis
Methamphetamine (MA)-associated psychosis has become a public concern. However, its mechanism is not clear. Investigating similarities and differences between MA-associated psychosis and schizophrenia in brain alterations would be informative for neuropathology.
Study Design
This study compared gray matter volumes of the brain across four participant groups: healthy controls (HC, n = 53), MA users without psychosis (MA, n = 22), patients with MA-associated psychosis (MAP, n = 34) and patients with schizophrenia (SCZ, n = 33). Clinical predictors of brain alterations, as well as association of brain alterations with psychotic symptoms and attention impairment were further investigated.
Study Results
Compared with the HC, the MAP and the SCZ showed similar gray matter reductions in the frontal cortex, particularly in prefrontal areas. Moreover, a stepwise extension of gray matter reductions was exhibited across the MA – MAP – SCZ. Duration of abstinence was associated with regional volumetric recovery in the MAP, while this amendment in brain morphometry was not accompanied with symptom’s remission. Illness duration of psychosis was among the predictive factors of regional gray matter reductions in both psychotic groups. Volume reductions were found to be associated with attention impairment in the SCZ, while this association was reversed in the MAP in frontal cortex.
Conclusions
This study suggested MA-associated psychosis and schizophrenia had common neuropathology in cognitive-related frontal cortices. A continuum of neuropathology between MA use and schizophrenia was tentatively implicated. Illness progressions and glial repairments could both play roles in neuropathological changes in MA-associated psychosis.
... 36 While models of self-administration in rodents are not equivalent to the human drug addiction experience, 37 complementing the above mostly preclinical efforts, several meta-analyses of GMV studies in human addiction facilitate the comparison between different drug classes. 6,7,9,10,38 These meta-analyses support the substance-general lower vmPFC grey matter estimates 6,7,9,10 and suggest several substance-specific patterns [e.g. lower NAcc grey matter estimates in alcohol, 6 and lower superior frontal gyrus grey matter estimates in cocaine addiction (relative to methamphetamine) 38 ]. ...
... 6,7,9,10,38 These meta-analyses support the substance-general lower vmPFC grey matter estimates 6,7,9,10 and suggest several substance-specific patterns [e.g. lower NAcc grey matter estimates in alcohol, 6 and lower superior frontal gyrus grey matter estimates in cocaine addiction (relative to methamphetamine) 38 ]. However, to the best of our knowledge, only two studies to date have directly assessed the overlapping and distinct neuroanatomical underpinnings related to opiate and psychostimulant use as they manifest in grey matter. ...
... The lower right IFG GMV in the CUD compared to the HUD group in our study, as also supported by the exploratory whole-brain analysis, agrees with extensive evidence for lower IFG GMV in chronic stimulant users compared to HC. 38,63,87,88 Given the wellestablished role of the right IFG in impulsivity and inhibitory control [32][33][34]89 and the higher impulsivity characterizing psychostimulant use disorder (cocaine 5,35,63 and methamphetamine 88 ), these results suggest a potential correlate in CUD for deficits in impulse control. Accordingly, we also report a trend for a CUD-specific positive correlation between the posterior putamen GMV and drug craving. ...
Different drugs of abuse impact the morphology of fronto-striatal dopaminergic targets in both common and unique ways. While dorsal striatal volume tracks with addiction severity across drug classes, opiates impact ventromedial prefrontal cortex (vmPFC) and nucleus accumbens (NAcc) neuroplasticity in preclinical models, and psychostimulants alter inhibitory control, rooted in cortical regions such as the inferior frontal gyrus (IFG). We hypothesized parallel gray matter volume (GMV) changes associated with human heroin or cocaine use disorder (HUD/CUD): lower GMV of vmPFC/NAcc in HUD and IFG in CUD, and putamen GMV to be associated with addiction severity measures (including craving) across both.
In this cross-sectional study, we quantified GMV (p < 0.05-corrected) in age/sex/IQ-matched individuals with HUD (n = 32; 7 women), CUD (n = 32; 6 women), and healthy controls (HC; n = 32; 6 women) and compared fronto-striatal volume between groups using voxelwise general linear models and non-parametric permutation based tests.
Overall, individuals with HUD had smaller vmPFC and NAcc/putamen volumes than HC. Bilateral lower IFG GMV patterns were specifically evident in CUD vs. HUD. Correlations between addiction severity measures and putamen GMV did not reach nominal significance level in this sample.
These results indicate alterations in dopamine-innervated regions (in the vmPFC and NAcc) in heroin addiction. For the first time we demonstrate lower IFG GMV specifically in CUD as compared to HUD, suggesting a signature of reduced inhibitory control, which remains to be tested directly using select behavioral measures. Overall, results suggest substance-specific volumetric changes in human psychostimulant or opiate addiction, with implications for fine-tuning biomarker and treatment identification by primary drug of abuse.
