RESUMO
Cocaine use is a major public health problem with serious negative consequences at both the individual and societal levels. Cocaine use disorder (CUD) is associated with cognitive and emotional impairments, often manifesting as alterations in brain functional connectivity (FC). This study employed resting-state functional magnetic resonance imaging (rs-fMRI) to examine dynamic FC in 38 male participants with CUD and 31 matched healthy controls. Using group spatial independent component analysis (group ICA) combined with sliding window approach, we identified two recurring distinct connectivity states: the strongly-connected state (state 1) and weakly-connected state (state 2). CUD patients exhibited significant increased mean dwell and fraction time in state 1, and increased transitions from state 2 to state 1, demonstrated significant strongly-connected state tendency. Our analysis revealed abnormal FC patterns that are state-dependent and state-shared in CUD patients. This study observed hyperconnectivity within the default mode network (DMN) and between DMN and other networks, which varied depending on the state. Furthermore, after adjustment for multiple comparisons, we found significant correlations between these altered dynamic FCs and clinical measures of impulsivity and borderline personality disorder. The disrupted FC and repetitive effects of precuneus and angular gyrus across correlations suggested that they might be the important hub of neural circuits related behaviorally and mentally in CUD. In summary, our study highlighted the potential of these disrupted FC as neuroimaging biomarkers and therapeutic targets, and provided new insights into the understanding of the neurophysiologic mechanisms of CUD.
Assuntos
Transtornos Relacionados ao Uso de Cocaína , Conectoma , Comportamento Impulsivo , Imageamento por Ressonância Magnética , Rede Nervosa , Humanos , Masculino , Transtornos Relacionados ao Uso de Cocaína/fisiopatologia , Transtornos Relacionados ao Uso de Cocaína/diagnóstico por imagem , Adulto , Comportamento Impulsivo/fisiologia , Rede Nervosa/fisiopatologia , Rede Nervosa/diagnóstico por imagem , Transtorno da Personalidade Borderline/fisiopatologia , Transtorno da Personalidade Borderline/diagnóstico por imagem , Rede de Modo Padrão/fisiopatologia , Rede de Modo Padrão/diagnóstico por imagem , Encéfalo/fisiopatologia , Encéfalo/diagnóstico por imagem , Pessoa de Meia-Idade , Adulto JovemRESUMO
AIMS: Cocaine Use Disorder (CUD) is an important health issue, associated with structural brain abnormalities. However, the impact of the route of administration and their predictive value for relapse remain unknown. METHODS: We conducted an anatomical MRI study in 55 CUD patients (26 CUD-Crack and 29 CUD-Hydro) entering inpatient detoxification, and 38 matched healthy controls. In patients, a 3-months outpatient follow-up was carried out to specify the treatment outcome status (relapser when cocaine was consumed once or more during the past month). A Voxel-Based Morphometry approach was used. RESULTS: Compared with controls, CUD patients had widespread gray matter alterations, mostly in frontal and temporal cortices, but also in the cerebellum and several sub-cortical structures. We then compared CUD-Crack with CUD-Hydro patients and found that crack-cocaine use was associated with lower volume in the right inferior and middle temporal gyri, and the right fusiform gyrus. Cerebellar vermis was smaller during detoxification in subsequent relapsers compared to three-months abstainers. CONCLUSIONS: Patients with CUD display widespread cortical and subcortical brain shrinkage. Patients with preferential crack-cocaine use and subsequent relapsers showed specific gray matter volume deficits, suggesting that different patterns of cocaine use and different clinical outcome are associated with different brain macrostructure.
Assuntos
Encéfalo , Transtornos Relacionados ao Uso de Cocaína , Substância Cinzenta , Imageamento por Ressonância Magnética , Humanos , Transtornos Relacionados ao Uso de Cocaína/diagnóstico por imagem , Transtornos Relacionados ao Uso de Cocaína/patologia , Masculino , Feminino , Adulto , Resultado do Tratamento , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Encéfalo/efeitos dos fármacos , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/patologia , Pessoa de Meia-Idade , Cocaína CrackRESUMO
Cocaine use disorder (CUD) is a global health problem with serious consequences for both individuals and society. Previous studies on abnormal anatomical patterns in CUD have mainly used voxel-based morphometry to investigate grey matter volume changes, while surface-based morphometry (SBM) has been found to provide detail information on cortical thickness (CT), surface area and cortical meancurve, which can contribute to a better understanding of structural brain changes associated with CUD. In this study, SBM was conducted to investigate abnormal neuroanatomical patterns in CUD and whether these abnormal patterns could be used as potential diagnostic biomarkers for CUD. Sixty-eight CUD individuals and 52 matched healthy controls were enrolled, and all participants performed once MRI scanning and clinical assessments. We found that CUD individuals exhibited altered morphological indicators across widespread brain regions and these abnormal anatomical alterations were significantly predictive of CUD status. Furthermore, the CT reduction of right insula was significantly associated with years of cocaine use in CUD. These findings revealed the association of abnormal anatomical patterns in specific brain regions in CUD, which further improve the understanding of CUD pathophysiology and provide the alternative diagnostic biomarkers for CUD.
Assuntos
Transtornos Relacionados ao Uso de Cocaína , Cocaína , Transtornos Relacionados ao Uso de Substâncias , Humanos , Encéfalo/diagnóstico por imagem , Transtornos Relacionados ao Uso de Cocaína/diagnóstico por imagem , Imageamento por Ressonância Magnética , BiomarcadoresRESUMO
Previous studies identified cerebral markers of response inhibition dysfunction in cocaine dependence. However, whether deficits in response inhibition vary with the severity of cocaine use or ameliorate during abstinence remain unclear. This study aimed to address these issues and the neural mechanisms supporting the individual variation. We examined the data of 67 individuals with cocaine dependence (CD) and 84 healthy controls (HC) who underwent functional magnetic resonance imaging during a stop-signal task (SST). The stop-signal reaction time (SSRT) was computed using the integration method, with a longer SSRT indicating poorer response inhibition. The results showed that, while CD and HC did not differ significantly in SSRT, years of cocaine use (YOC) and days of abstinence (DOA) were each positively and negatively correlated with the SSRT in CD. Whole-brain regressions of stop minus go success trials on SSRT revealed correlates in bilateral superior temporal gyrus (STG) in response inhibition across CD and HC. Further, mediation and path analyses revealed that YOC and DOA affected SSRT through the STG activities in CD. Together, the findings characterized the contrasting effects of cocaine use severity and abstinence on response inhibition as well as the neural processes that support these effects in cocaine dependence.
Assuntos
Transtornos Relacionados ao Uso de Cocaína , Cocaína , Humanos , Transtornos Relacionados ao Uso de Cocaína/diagnóstico por imagem , Tempo de Reação/fisiologia , Encéfalo/diagnóstico por imagem , Inibição Psicológica , Cocaína/efeitos adversosRESUMO
Influential accounts of addiction posit alterations in adaptive behavior driven by deficient dopaminergic prediction errors (PEs), signaling the discrepancy between actual and expected reward. Dopamine neurons encode these error signals in subjective terms, calibrated by individual risk preferences, as "utility" PEs. It remains unclear, however, whether people with drug addiction have PE deficits or their computational source. Here, using an analogous task to prior single-unit studies with known expectancies, we show that fMRI-measured PEs similarly reflect utility PEs. Relative to control participants, people with chronic cocaine addiction demonstrate reduced utility PEs in the dopaminoceptive ventral striatum, with similar trends in orbitofrontal cortex. Dissecting this PE signal into its subcomponent terms attributed these reductions to weaker striatal responses to received reward/utility, whereas suppression of activity with reward expectation was unchanged. These findings support that addiction may fundamentally disrupt PE signaling and reveal an underappreciated role for perceived reward value in this mechanism.
Assuntos
Transtornos Relacionados ao Uso de Cocaína , Estriado Ventral , Humanos , Transtornos Relacionados ao Uso de Cocaína/diagnóstico por imagem , Recompensa , Córtex Pré-Frontal/fisiologia , Neostriado , Imageamento por Ressonância MagnéticaRESUMO
BACKGROUND: Previous studies have focused on both ventral striatum (VS) and dorsal striatum (DS) in characterizing dopaminergic deficits in addiction. Animal studies suggest VS and DS dysfunction each in association with impulsive and compulsive cocaine use during early and later stages of addiction. However, few human studies have aimed to distinguish the roles of VS and DS dysfunction in cocaine misuse. METHODS: We examined VS and DS resting-state functional connectivity (rsFC) of 122 recently abstinent cocaine-dependent individuals (CDs) and 122 healthy controls (HCs) in 2 separate cohorts. We followed published routines in imaging data analyses and evaluated the results at a corrected threshold with age, sex, years of drinking, and smoking accounted for. RESULTS: CDs relative to HCs showed higher VS rsFC with the left inferior frontal cortex (IFC), lower VS rsFC with the hippocampus, and higher DS rsFC with the left orbitofrontal cortex. Region-of-interest analyses confirmed the findings in the 2 cohorts examined separately. In CDs, VS-left IFC and VS-hippocampus connectivity was positively and negatively correlated with average monthly cocaine use in the prior year, respectively. In the second cohort where participants were assessed with the Barratt Impulsivity Scale (BIS-11), VS-left IFC and VS-hippocampus connectivity was also positively and negatively correlated with BIS-11 scores in CDs. In contrast, DS-orbitofrontal cortex connectivity did not relate significantly to cocaine use metrics or BIS-11 scores. CONCLUSION: These findings associate VS rsFC with impulsivity and the severity of recent cocaine use. How DS connectivity partakes in cocaine misuse remains to be investigated.
Assuntos
Transtornos Relacionados ao Uso de Cocaína , Cocaína , Estriado Ventral , Humanos , Transtornos Relacionados ao Uso de Cocaína/diagnóstico por imagem , Comportamento Impulsivo , Estriado Ventral/diagnóstico por imagem , Córtex Pré-Frontal , Imageamento por Ressonância MagnéticaRESUMO
OBJECTIVE: Chronic substance use and its effects on brain function and structure has long been of interest to clinicians and researchers. Prior cross-sectional comparisons of diffusion tensor imaging (DTI) metrics have suggested deleterious effects of chronic substance use (i.e., cocaine use) on white matter coherence. However, it is unclear how these effects may replicate across geographic regions when examined with similar technologies. In this study, we sought to conduct a replication of previous work in this area and determine whether there are any patterns of persistent differences in white matter microstructure between individuals with a history of cocaine use disorder (CocUD, according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) and healthy controls. METHOD: A total of 46 participants (21 healthy controls, 25 chronic cocaine users) were recruited from the Richmond, Virginia metropolitan area. Information regarding past and current substance use was collected from all participants. Participants also completed structural and DTI scans. RESULTS: Consistent with previous DTI studies, significant differences were found between fractional anisotropy (FA) and axial diffusivity (AD) CocUD and controls, with CocUD showing lower FA and AD in the right inferior and superior longitudinal fasciculus, the genu, body, and splenium of the corpus callosum, and the anterior, posterior, and superior corona radiata, among several other regions. These differences were not significant for other diffusivity metrics. Lifetime alcohol consumption was greater in the CocUD group, but lifetime alcohol consumption did not show a significant linear relationship with any of the DTI metrics in within-group regression analyses. CONCLUSIONS: These data align with previously reported declines in white matter coherence in chronic cocaine users. However, it is less clear whether comorbid alcohol consumption results in an additive deleterious effect on white matter microstructure.
Assuntos
Transtornos Relacionados ao Uso de Cocaína , Imagem de Tensor de Difusão , Substância Branca , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Consumo de Bebidas Alcoólicas/epidemiologia , Consumo de Bebidas Alcoólicas/patologia , Bebidas Alcoólicas/análise , Anisotropia , Estudos de Casos e Controles , Transtornos Relacionados ao Uso de Cocaína/diagnóstico por imagem , Transtornos Relacionados ao Uso de Cocaína/epidemiologia , Transtornos Relacionados ao Uso de Cocaína/patologia , Comorbidade , Corpo Caloso/diagnóstico por imagem , Corpo Caloso/patologia , Tratos Piramidais/diagnóstico por imagem , Tratos Piramidais/patologia , Análise de Regressão , Virginia/epidemiologia , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Doença Crônica/epidemiologiaRESUMO
Cocaine use is disproportionately prevalent in people with HIV (PWH) and is known to potentiate HIV neuropathogenesis. As both HIV and cocaine have well-documented cortico-striatal effects, PWH who use cocaine and have a history of immunosuppression may exhibit greater FC deficits compared to PWH without these conditions. However, research investigating the legacy effects of HIV immunosuppression (i.e., a history of AIDS) on cortico-striatal functional connectivity (FC) in adults with and without cocaine use is sparse. Resting-state functional magnetic resonance imaging (fMRI) and neuropsychological assessment data from 273 adults were analyzed to examine FC in relation to HIV disease: HIV-negative (n = 104), HIV-positive with nadir CD4 ≥ 200 (n = 96), HIV-positive with nadir CD4 < 200 (AIDS; n = 73), and cocaine use (83 COC and 190 NON). Using independent component analysis/dual regression, FC was assessed between the basal ganglia network (BGN) and five cortical networks: dorsal attention network (DAN), default mode network, left executive network, right executive network, and salience network. There were significant interaction effects such that AIDS-related BGN-DAN FC deficits emerged in COC but not in NON participants. Independent of HIV, cocaine effects emerged in FC between the BGN and executive networks. Disruption of BGN-DAN FC in AIDS/COC participants is consistent with cocaine potentiation of neuro-inflammation and may be indicative of legacy HIV immunosuppressive effects. The current study bolsters previous findings linking HIV and cocaine use with cortico-striatal networking deficits. Future research should consider the effects of the duration of HIV immunosuppression and early treatment initiation.
Assuntos
Síndrome da Imunodeficiência Adquirida , Transtornos Relacionados ao Uso de Cocaína , Cocaína , Infecções por HIV , Adulto , Humanos , Imageamento por Ressonância Magnética/métodos , Síndrome da Imunodeficiência Adquirida/complicações , Transtornos Relacionados ao Uso de Cocaína/complicações , Transtornos Relacionados ao Uso de Cocaína/diagnóstico por imagem , Infecções por HIV/complicações , Infecções por HIV/diagnóstico por imagem , Mapeamento Encefálico/métodos , EncéfaloRESUMO
Cocaine use is a major public health problem with significant negative consequences at the individual and societal levels. Cocaine use disorder (CUD) is closely associated with brain structure alterations, which are mainly analyzed using voxel-based morphometric and traditional volumetric methods with certain limitations. This study conducted vertex-wise shape analysis to examine the effects of cocaine use on surface-based alterations of the basal ganglia in CUD. A total of 68 CUD individuals and 52 matched healthy controls (HCs) were enrolled in the study and underwent MRI scans and clinical measures. There were no significant differences in the volume of brain tissues and subcortical structures between groups. Related to HCs, CUD individuals showed regional surface atrophy of the left medial anterior thalamus, right medial posterior thalamus, and right dorsal anterior caudate, which were found to exhibit more significant surface atrophy in CUD individuals with onset age of cocaine use below 18. Furthermore, surface-based alteration of the right dorsal anterior caudate was significantly associated with years of cocaine use and the onset age of cocaine use in CUD individuals. Furthermore, both CUD individuals with onset age of cocaine use below 18 and CUD individuals with onset age of cocaine use above 18 showed similar significant relationship patterns between regional surface alteration of right dorsal anterior caudate and the onset age of cocaine use. These findings shed light on the effect of cocaine use on basal ganglia, help us understand the neural basis of cocaine dependence, and further provide effective interventions for CUD.
Assuntos
Transtornos Relacionados ao Uso de Cocaína , Cocaína , Humanos , Gânglios da Base/diagnóstico por imagem , Encéfalo , Transtornos Relacionados ao Uso de Cocaína/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodosRESUMO
The habenula (Hb) is central to adaptive reward- and aversion-driven behaviors, comprising a hub for higher-order processing networks involving the prefrontal cortex (PFC). Despite an established role in preclinical models of cocaine addiction, the translational significance of the Hb and its connectivity with the PFC in humans is unclear. Using diffusion tractography, we detailed PFC structural connectivity with the Hb and two control regions, quantifying tract-specific microstructural features in healthy and cocaine-addicted individuals. White matter was uniquely impaired in PFC-Hb projections in both short-term abstainers and current cocaine users. Abnormalities in this tract further generalized to an independent sample of heroin-addicted individuals and were associated, in an exploratory analysis, with earlier onset of drug use across the addiction subgroups, potentially serving as a predisposing marker amenable for early intervention. Importantly, these findings contextualize a plausible PFC-Hb circuit in the human brain, supporting preclinical evidence for its impairment in cocaine addiction.
Assuntos
Transtornos Relacionados ao Uso de Cocaína , Cocaína , Habenula , Dependência de Heroína , Humanos , Transtornos Relacionados ao Uso de Cocaína/diagnóstico por imagem , Imageamento por Ressonância Magnética , Córtex Pré-Frontal/diagnóstico por imagemRESUMO
Evidence from animal research, postmortem analyses, and magnetic resonance imaging (MRI) investigations indicate substantial morphological alteration in brain structure as a function of human immunodeficiency virus (HIV) or cocaine dependence (CD). Although previous research on HIV+ active cocaine users suggests the presence of deleterious morphological effects in excess of either condition alone, a yet unexplored question is whether there is a similar deleterious interaction in HIV+ individuals with CD who are currently abstinent. To this end, the combinatorial effects of HIV and CD history on regional brain volume, cortical thickness, and neurocognitive performance was examined across four groups of participants in an exploratory study: healthy controls (n = 34), HIV-negative individuals with a history of CD (n = 21), HIV+ individuals with no history of CD (n = 20), HIV+ individuals with a history of CD (n = 15). Our analyses revealed no statistical evidence of an interaction between both conditions on brain morphometry and neurocognitive performance. While descriptively, individuals with comorbid HIV and a history of CD exhibited the lowest neurocognitive performance scores, using Principle Component Analysis of neurocognitive testing data, HIV was identified as the primary driver of neurocognitive impairment. Higher caudate volume was evident in CD+ participants relative to CD- participants. Findings indicate no evidence of compounded differences in neurocognitive function or structural measures of brain integrity in HIV+ individuals in recovery from CD relative to individuals with only one condition.
Assuntos
Transtornos Relacionados ao Uso de Cocaína , Cocaína , Infecções por HIV , Humanos , Transtornos Relacionados ao Uso de Cocaína/diagnóstico por imagem , Transtornos Relacionados ao Uso de Cocaína/psicologia , Testes Neuropsicológicos , Infecções por HIV/complicações , Infecções por HIV/diagnóstico por imagem , Infecções por HIV/patologia , Encéfalo/patologia , Imageamento por Ressonância MagnéticaRESUMO
Previous brain imaging studies with chronic cocaine users (CU) using diffusion tensor imaging (DTI) mostly focused on fractional anisotropy to investigate white matter (WM) integrity. However, a quantitative interpretation of fractional anisotropy (FA) alterations is often impeded by the inherent limitations of the underlying tensor model. A more fine-grained measure of WM alterations could be achieved by measuring fibre density (FD). This study investigates this novel DTI metric comparing 23 chronic CU and 32 healthy subjects. Quantitative hair analysis was used to determine intensity of cocaine and levamisole exposure-a cocaine adulterant with putative WM neurotoxicity. We first assessed the impact of cocaine use, levamisole exposure and alcohol use on group differences in WM integrity. Compared with healthy controls, all models revealed cortical reductions of FA and FD in CU. At the within-patient group level, we found that alcohol use and levamisole exposure exhibited regionally different FA and FD alterations than cocaine use. We found mostly negative correlations of tract-based WM associated with levamisole and weekly alcohol use. Specifically, levamisole exposure was linked with stronger WM reductions in the corpus callosum than alcohol use. Cocaine use duration correlated negatively with FA and FD in some regions. Yet, most of these correlations did not survive a correction for multiple testing. Our results suggest that chronic cocaine use, levamisole exposure and alcohol use were all linked to significant WM impairments in CU. We conclude that FD could be a sensitive marker to detect the impact of the use of multiple substances on WM integrity in cocaine but also other substance use disorders.
Assuntos
Transtornos Relacionados ao Uso de Cocaína , Cocaína , Substância Branca , Adulto , Anisotropia , Encéfalo/diagnóstico por imagem , Transtornos Relacionados ao Uso de Cocaína/diagnóstico por imagem , Imagem de Tensor de Difusão/métodos , Etanol , Humanos , Levamisol , Substância Branca/diagnóstico por imagemRESUMO
While it has been suggested that cocaine use and relapse in women is more strongly related to stress-relief craving, whereas cocaine use in men is more strongly related to reward craving, the neural mechanisms that underlie these differences are poorly understood. The aim of this study was to investigate sex-dependent differences in insular morphometry and associations with craving, in a sample of regular cocaine users (CUs) and non-drug using controls (non-CUs). It was hypothesized that insular volume, thickness and surface area would be lower in CU women, compared with CU men and non-CUs. It was furthermore hypothesized that insular morphometry, particularly insular thickness, would be negatively associated to reward craving in CU men, while being negatively associated with stress-relief craving in CU women. In contrast to the hypothesis, we did not find evidence of sex-specific differences in insular morphometry in CUs. However, sex-specific association between stress-relief craving and insular morphometry were found: Right insular volume was negatively associated with stress-relief craving in CU women, whereas this association was positive in CU men. Additionally, right insular surface area was negatively associated with stress-relief craving in cocaine-using men, whereas this association was positive in cocaine-using women. In conclusion, the current study provides first evidence of sex-specific differences in the association between craving and insular morphometry in a sample of regular cocaine users. Although speculative, these sex-specific alterations in insular morphometry may underlie higher stress-induced craving and relapse in CU women compared with CU men.
Assuntos
Transtornos Relacionados ao Uso de Cocaína , Cocaína , Transtornos Relacionados ao Uso de Cocaína/diagnóstico por imagem , Fissura , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Caracteres SexuaisRESUMO
Individuals with a diagnosis of co-morbid HIV infection and cocaine use disorder are at higher risk of poor health outcomes. Active cocaine users, both with and without HIV infection, show clear deficits in response inhibition and other measures of executive function that are instrumental in maintaining drug abstinence, factors that may complicate treatment. Neuroimaging and behavioral evidence indicate normalization of executive control processes in former cocaine users as a function of the duration of drug abstinence, but it is unknown to what extent co-morbid diagnosis of HIV affects this process. To this end, we investigate the combinatorial effects of HIV and cocaine dependence on the neural substrates of cognitive control in cocaine-abstinent individuals with a history of cocaine dependence. Blood-oxygen level dependent signal changes were measured as 86 participants performed a Go/NoGo response inhibition task while undergoing functional magnetic resonance imaging (fMRI). Four groups of participants were selected based on HIV and cocaine-dependence status. Participants affected by both conditions demonstrated the lowest response accuracy of all participant groups. In a region of interest analysis, hyperactivation in the left putamen and midline-cingulate hyperactivation was observed in individuals with both HIV and cocaine dependence relative to individuals with only one condition. Results of a whole-brain analysis indicate response inhibition-related hyperactivation in the bilateral supplementary motor area, bilateral hippocampi, bilateral primary somatosensory areas, right dorsal anterior cingulate, and left insula in the CD+/HIV+ group relative to all other groups. These results indicate complex and interactive alterations in neural activation during response inhibition and highlight the importance of examining the neurocognitive effects of co-morbid conditions.
Assuntos
Transtornos Relacionados ao Uso de Cocaína/diagnóstico por imagem , Cognição/fisiologia , Neuroimagem Funcional/métodos , Infecções por HIV/diagnóstico por imagem , Inibição Psicológica , Tempo de Reação/fisiologia , Adulto , Transtornos Relacionados ao Uso de Cocaína/epidemiologia , Transtornos Relacionados ao Uso de Cocaína/psicologia , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/psicologia , Humanos , Masculino , Testes de Estado Mental e Demência , Pessoa de Meia-Idade , Desempenho Psicomotor/fisiologiaRESUMO
Gray matter volume (GMV) in frontal cortical and limbic regions is susceptible to cocaine-associated reductions in cocaine-dependent individuals (CD) and is negatively associated with duration of cocaine use. Gender differences in CD individuals have been reported clinically and in the context of neural responses to cue-induced craving and stress reactivity. The variability of GMV in select brain areas between men and women (e.g., limbic regions) underscores the importance of exploring interaction effects between gender and cocaine dependence on brain structure. Therefore, voxel-based morphometry data derived from the ENIGMA Addiction Consortium were used to investigate potential gender differences in GMV in CD individuals compared to matched controls (CTL). T1-weighted MRI scans and clinical data were pooled from seven sites yielding 420 gender- and age-matched participants: CD men (CDM, n = 140); CD women (CDW, n = 70); control men (CTLM, n = 140); and control women (CTLW, n = 70). Differences in GMV were assessed using a 2 × 2 ANCOVA, and voxelwise whole-brain linear regressions were conducted to explore relationships between GMV and duration of cocaine use. All analyses were corrected for age, total intracranial volume, and site. Diagnostic differences were predominantly found in frontal regions (CD < CTL). Interestingly, gender × diagnosis interactions in the left anterior insula and left lingual gyrus were also documented, driven by differences in women (CDW < CTLW). Further, lower right hippocampal GMV was associated with greater cocaine duration in CDM. Given the importance of the anterior insula to interoception and the hippocampus to learning contextual associations, results may point to gender-specific mechanisms in cocaine addiction.
Assuntos
Córtex Cerebral/patologia , Transtornos Relacionados ao Uso de Cocaína/patologia , Substância Cinzenta/patologia , Imageamento por Ressonância Magnética , Neuroimagem , Caracteres Sexuais , Adulto , Córtex Cerebral/diagnóstico por imagem , Transtornos Relacionados ao Uso de Cocaína/diagnóstico por imagem , Feminino , Substância Cinzenta/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Delay discounting has been proposed as a behavioral marker of substance use disorders. Innovative analytic approaches that integrate information from multiple neuroimaging modalities can provide new insights into the complex effects of drug use on the brain. This study implemented a supervised multimodal fusion approach to reveal neural networks associated with delay discounting that distinguish persons with and without cocaine use disorder (CUD). METHODS: Adults with (n = 35) and without (n = 37) CUD completed a magnetic resonance imaging (MRI) scan to acquire high-resolution anatomical, resting-state functional, and diffusion-weighted images. Pre-computed features from each data modality included whole-brain voxel-wise maps for gray matter volume, fractional anisotropy, and regional homogeneity, respectively. With delay discounting as the reference, multimodal canonical component analysis plus joint independent component analysis was used to identify co-alterations in brain structure and function. RESULTS: The sample was 58% male and 78% African-American. As expected, participants with CUD had higher delay discounting compared to those without CUD. One joint component was identified that correlated with delay discounting across all modalities, involving regions in the thalamus, dorsal striatum, frontopolar cortex, occipital lobe, and corpus callosum. The components were negatively correlated with delay discounting, such that weaker loadings were associated with higher discounting. The component loadings were lower in persons with CUD, meaning the component was expressed less strongly. CONCLUSIONS: Our findings reveal structural and functional co-alterations linked to delay discounting, particularly in brain regions involved in reward salience, executive control, and visual attention and connecting white matter tracts. Importantly, these multimodal networks were weaker in persons with CUD, indicating less cognitive control that may contribute to impulsive behaviors.
Assuntos
Encéfalo/diagnóstico por imagem , Transtornos Relacionados ao Uso de Cocaína/diagnóstico por imagem , Transtornos Relacionados ao Uso de Cocaína/psicologia , Desvalorização pelo Atraso/fisiologia , Imageamento por Ressonância Magnética/métodos , Adulto , Encéfalo/metabolismo , Transtornos Relacionados ao Uso de Cocaína/sangue , Desvalorização pelo Atraso/efeitos dos fármacos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Previous investigations have used global graph theory measures in order to disentangle the complexity of the neural reorganizations occurring in cocaine use disorder (CUD). However, how these global topological alterations map into individual brain network areas remains unknown. In this study, we used resting state functional magnetic resonance imaging (fMRI) data to investigate node-level topological dysfunctions in CUD. The sample was composed of 32 individuals with CUD and 32 healthy controls, matched in age, years of education and intellectual functioning. Graph theory measures of optimal connectivity distance, node strength, nodal efficiency and clustering coefficient were estimated in each participant using voxel-wise functional connectivity connectomes. CUD individuals as compared with healthy controls showed higher optimal connectivity distances in ventral striatum, insula, cerebellum, temporal cortex, lateral orbitofrontal cortex, middle frontal cortex and left hippocampus. Furthermore, clinical measures quantifying severity of dependence were positively related with optimal connectivity distances in the right rolandic operculum and the right lateral orbitofrontal cortex, whereas length of abstinence was negatively associated with optimal connectivity distances in the right temporal pole and the left insula. Our results reveal a topological distancing of cognitive and affective related areas in addiction, suggesting an overall reduction in the communication capacity of these regions.
Assuntos
Encéfalo/patologia , Transtornos Relacionados ao Uso de Cocaína/patologia , Adulto , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Transtornos Relacionados ao Uso de Cocaína/diagnóstico por imagem , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Gravidade do PacienteRESUMO
Reduced empathic abilities are frequently observed in drug abusers. These deficits may compromise interpersonal interactions and contribute to diminished social functioning. However, previous evidence regarding empathy and addiction is behaviorally unspecific and virtually null in terms of their brain structural or functional correlates. Moreover, no previous study has investigated how empathy is affected by drugs whose consumption is particularly characterized by counter-empathic behaviors. Here, we conducted the first assessment of neurocognitive correlates of empathy for pain in dependent users (predominantly men) of smoked cocaine (SC, coca paste, n = 37). We compared their performance in the empathy task with that of two groups matched in relevant demographic variables: 24 dependent users of insufflated cocaine hydrochloride (CC) and 21 healthy controls. In addition, we explored the structural anatomy and functional connectivity (FC) correlates of empathic impairments across groups. Our results showed that, compared to CC and controls, SC users exhibited a selective reduction of empathic concern for intentional harms. These impairments were associated with lower gray matter volumes in regions subserving social cognition (i.e., right inferior parietal lobule, supramarginal and angular gyri). Furthermore, reduced empathic concern correlated with FC within affective empathy and social cognition networks, which are also linked to cognitive changes reported in addiction (i.e., inferior frontal and orbital gyri, posterior insula, supplementary motor area, cingulate cortex). Our findings suggest that chronic consumption of SC may involve reduced empathic concern and relevant neuroanatomical and FC abnormalities, which, in turn, may result in social interaction dysfunction. These results can inform theoretical and applied developments in neuropsychopharmacology.
Assuntos
Encéfalo/diagnóstico por imagem , Fumar Cocaína/psicologia , Transtornos Relacionados ao Uso de Cocaína/diagnóstico por imagem , Transtornos Relacionados ao Uso de Cocaína/psicologia , Empatia/efeitos dos fármacos , Rede Nervosa/diagnóstico por imagem , Adolescente , Encéfalo/efeitos dos fármacos , Cocaína/administração & dosagem , Cocaína/efeitos adversos , Fumar Cocaína/efeitos adversos , Empatia/fisiologia , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Rede Nervosa/efeitos dos fármacos , Estimulação Luminosa/métodos , Adulto JovemRESUMO
BACKGROUND: Cocaine addiction is associated with altered sensitivity to natural reinforcers and intense drug craving. However, previous findings on reward-related responses were mixed, and few studies have examined whether reward responses relate to tonic cocaine craving. METHODS: We combined functional magnetic resonance imaging and a monetary incentive delay task to investigate these issues. Imaging data were processed with published routines, and the results were evaluated with a corrected threshold. We compared reward responses of 50 cocaine-dependent individuals (CDs) and 45 healthy controls (HCs) for the ventral striatum (VS) and the whole brain. We also examined the regional responses in association with tonic cocaine craving, as assessed by the Cocaine Craving Questionnaire (CCQ) in CDs. We performed mediation analyses to evaluate the relationship between regional responses, CCQ score, and recent cocaine use. RESULTS: The VS showed higher activation to large as compared with small or no wins, but this reward-related activity did not differ between CDs and HCs. The precentral gyrus (PCG), anterior insula, and supplementary motor area showed higher activation during large vs no wins in positive correlation with the CCQ score in CDs. Mediation analyses suggested that days of cocaine use in the prior month contributed to higher CCQ scores and, in turn, PCG reward responses. CONCLUSIONS: The results highlight a unique relationship between reward responses of the primary motor cortex, tonic cocaine craving, and recent cocaine use. The motor cortex may partake in the cognitive motor processes critical to drug-seeking behavior in addicted individuals.
Assuntos
Córtex Cerebral/fisiopatologia , Transtornos Relacionados ao Uso de Cocaína/fisiopatologia , Fissura/fisiologia , Desvalorização pelo Atraso/fisiologia , Motivação/fisiologia , Recompensa , Estriado Ventral/fisiopatologia , Adulto , Córtex Cerebral/diagnóstico por imagem , Transtornos Relacionados ao Uso de Cocaína/diagnóstico por imagem , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Córtex Motor/diagnóstico por imagem , Córtex Motor/fisiopatologia , Estriado Ventral/diagnóstico por imagemRESUMO
A threefold increase in fatal cocaine overdoses during the past decade highlights the critical lack of medications for cocaine use disorders. The brain response to drug cues can predict future drug use; however, results have been mixed. We present preliminary evidence that a sustained response to repeated cocaine cues within a single task is a significant predictor of drug-use outcomes. Seventy-three cocaine inpatients were administered a passive-viewing fMRI task, featuring 500 ms novel evocative (cocaine, sexual, aversive) and neutral comparator cues in the first half (Half1), which were then repeated in the second half (Half2). After the baseline scan, patients received eight outpatient treatment weeks with twice-weekly drug screens. Drug-use outcome groups were empirically defined based on cocaine-positive or missing urines averaged across the outpatient phase: GOOD (<40%), POOR (>85%), and Intermediate (INT, between 40% and 85%) outcomes. Differences of response to initial (Half1) and repeated (Half2) cues in a priori (cue-reactive) regions were tested between outcome groups (3 [Group] × 2 [Halves] ANOVA). An interaction was found in the brain response to drug (but not sex or aversive) cues, with a significant difference between the GOOD and POOR outcome groups in Half2, driven by a significant decrease in brain response by the GOOD outcome group and a sustained brain response by the POOR outcome group, to repeated cocaine cues. The brain response to repeated drug cues may be a useful predictor of future drug use, encouraging future intervention studies to restore a "healthy" (decreasing) response to the repeated presentation of drug cues.