Distance disintegration characterizes node-level topological dysfunctions in cocaine addiction.

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.

Left frontoparietal network activity is modulated by drug stimuli in cocaine addiction.

Cocaine addicts present reduced activity in the left frontoparietal network, a brain network associated with cognitive control, during the processing of non-drug reward related stimuli (Costumero et al., Addiction Biology 22:479-489, 2015). However, the involvement of this network in drug-related stimuli processing remains unclear. Here, fifteen cocaine-dependent men and fifteen healthy matched controls viewed cocaine-related, erotic, aversive, and neutral pictures during an fMRI session. Group independent component analysis was then performed to investigate how functional networks were modulated by the different emotional images. The results showed that the cocaine-dependent group showed stronger left frontoparietal network activity during the processing of cocaine-related pictures than the control group. Furthermore, the activity of this network during cocaine image processing was positively associated with the years of cocaine use in addicted subjects. In conclusion, our results indicate that the left frontoparietal network is affected in cocaine-dependent men, and may be related to the cognitive control deficits shown in addiction.

Reduced activity in functional networks during reward processing is modulated by abstinence in cocaine addicts.

Cocaine addiction is characterized by alterations in motivational and cognitive processes. Recent studies have shown that some alterations present in cocaine users may be related to the activity of large functional networks. The aim of this study was to investigate how these functional networks are modulated by non-drug rewarding stimuli in cocaine-dependent individuals. Twenty abstinent cocaine-dependent and 21 healthy matched male controls viewed erotic and neutral pictures while undergoing a functional magnetic resonance imaging scan. Group independent component analysis was then performed in order to investigate how functional networks were modulated by reward in cocaine addicts. The results showed that cocaine addicts, compared with healthy controls, displayed diminished modulation of the left frontoparietal network in response to erotic pictures, specifically when they were unpredicted. Additionally, a positive correlation between the length of cocaine abstinence and the modulation of the left frontoparietal network by unpredicted erotic images was found. In agreement with current addiction models, our results suggest that cocaine addiction contributes to reduce sensitivity to rewarding stimuli and that abstinence may mitigate this effect.

Abstinence duration modulates striatal functioning during monetary reward processing in cocaine patients.

Pre-clinical and clinical studies in cocaine addiction highlight alterations in the striatal dopaminergic reward system that subserve maintenance of cocaine use. Using an instrumental conditioning paradigm with monetary reinforcement, we studied striatal functional alterations in long-term abstinent cocaine-dependent patients and striatal functioning as a function of abstinence and treatment duration. Eighteen patients and 20 controls underwent functional magnetic resonance imaging during a Monetary Incentive Delay task. Region of interest analyses based on masks of the dorsal and ventral striatum were conducted to test between-group differences and the functional effects in the cocaine group of time (in months) with no more than two lapses from the first time patients visited the clinical service to seek treatment at the scanning time (duration of treatment), and the functional effects of the number of months with no lapses or relapses at the scanning session time (length of abstinence). We applied a voxel-wise and a cluster-wise FWE-corrected level (pFWE) at a threshold of P < 0.05. The patient group showed lower activation in the right caudate during reward anticipation than the control group. The regression analyses in the patients group revealed a positive correlation between duration of treatment and brain activity in the left caudate during reward anticipation. Likewise, length of abstinence negatively correlated with brain activity in the bilateral nucleus accumbens during monetary outcome processing. In conclusion, caudate and nucleus accumbens show a different brain response pattern to non-drug rewards during cocaine addiction, which can be modulated by treatment success.

Lower activation in the right frontoparietal network during a counting Stroop task in a cocaine-dependent group.

Dysregulation in cognitive control networks may mediate core characteristics of drug addiction. Cocaine dependence has been particularly associated with low activation in the frontoparietal regions during conditions requiring decision making and cognitive control. This functional magnetic resonance imaging (fMRI) study aimed to examine differential brain-related activation to cocaine addiction during an inhibitory control paradigm, the "Counting" Stroop task, given the uncertainties of previous studies using positron emission tomography. Sixteen comparison men and 16 cocaine-dependent men performed a cognitive "Counting" Stroop task in a 1.5T Siemens Avanto. The cocaine-dependent patient group and the control group were matched for age, level of education and general intellectual functioning. Groups did not differ in terms of the interference measures deriving from the counting Stroop task. Moreover, the cocaine-dependent group showed lower activation in the right inferior frontal gyrus, the right inferior parietal gyrus and the right superior temporal gyrus than the control group. Cocaine patients did not show any brain area with increased activation when compared with controls. In short, Stroop-interference was accompanied by lower activation in the right frontoparietal network in cocaine-dependent patients, even in the absence of inter-group behavioral differences. Our study is the first application of a counting Stroop task using fMRI to study cocaine dependence and yields results that corroborate the involvement of a frontoparietal network in the neural changes associated with attentional interference deficits in cocaine-dependent men.

Reduced striatal volume in cocaine-dependent patients.

Long-term cocaine consumption is associated with brain structural and functional changes. While the animal literature on cocaine use and dependence has traditionally focused on the striatum, previous human studies using voxel-based morphometry have reported reduced volumes of gray matter in several brain areas, but not in the striatum. Brain magnetic resonance imaging was performed with 20 cocaine-dependent patients and 16 healthy age-, education- and intelligence-matched control men. The cocaine-dependent group had lower gray matter volumes in the striatum and right supramarginal gyrus compared to controls. Within the cocaine-dependent group, years of cocaine use were inversely associated with the volume of the bilateral middle frontal gyrus, left superior frontal gyrus, parahippocampus, posterior cingulate, amygdala, insula, right middle temporal gyrus and cerebellum. These results show that cocaine dependence is associated with reduced gray matter volumes in the target structures of the dopaminergic system. These findings are the first to suggest reduced gray matter in the striatum by means of voxel-based morphometry in human users, thereby linking human results to animal models of addiction. In addition, the relationship between years of use and gray matter volumes in numerous brain regions are consistent with these volume reductions arising as a consequence of the cocaine use.

Right parietal hypoactivation in a cocaine-dependent group during a verbal working memory task.

It has been suggested that cocaine addiction affects the engagement of the frontoparietal networks in executive functions, such as attention and working memory. Thus, our objective was to investigate brain differences between cocaine-dependent subjects and healthy controls during the performance of a verbal working memory task. Nineteen comparison men and nineteen cocaine-dependent men performed a 2-back task. Data were acquired on a 1.5-T Siemens Avanto. Image processing and statistical analyses were carried out using SPM5; Biological Parametric Mapping (BPM) was used for further morphometric and correlation analyses. No performance differences were found between groups. However, the dorsal part of the right inferior parietal cortex (BA 40) was less activated in the cocaine-dependent group. Cocaine patients did not overactive any brain area when compared with controls. Our results show reduced activation in the brain areas related to the attention system in cocaine-dependent men while performing a verbal working memory task. Chronic cocaine use may affect the attentional system in the right parietal lobe, making patients more prone to attentional deficits.

Interacciones y consecuencias del consumo combinado de alcohol y cocaína: una actualización sobre el cocaetileno1 / Interactions and consequences of the combined use of alcohol and cocaine: an update on cocaethylene

Los pacientes que solicitan tratamiento por consumo de cocaína y abuso de alcohol, presentan peculiaridades respecto de los que sólo consumen cocaína. La ingesta de alcohol como detonante del “craving” y conducta de búsqueda compulsiva de cocaína, influye en haber una mayor perdida de control del consumo, más problemas sociales, más conductas de riesgo y antisociales. Hipótesis: la presencia de un metabolito denominado Cocaetileno, resultante del consumo simultaneo de alcohol y cocaína, podría explicar, la mayor toxicidad y compulsividad de estos episodios. Metodología: Se realiza una revisión de la literatura científica sobre las consecuencias de la interacción alcohol-cocaína. Resultados: La interacción metabólica alcohol-cocaína incrementa el potencial tóxico de ambas sustancias por separado. El cocaetileno actúa como tóxico per se. Su presencia en el organismo provoca mayor riesgo potencial en los consumo simultáneos de alcohol y cocaína. Existen concentraciones de cocaetileno más significativas cuando el alcohol se administra previamente a la cocaína. Los resultados de la investigación básica muestran que, gran parte de las diferencias observadas en la acción de ambas sustancias, cuando se ingieren conjuntamente, pudieran estar debidas a modificaciones en la farmacocinética de dichas drogas y a la potencial acción del cocaetileno lo que, sumado a las respectivas acciones del alcohol y la cocaína, podría ser la base de la mayor gravedad de los cuadros clínicos observados (AU)

Patients who request treatment for cocaine use and alcohol abuse present differences from those who use cocaine only. Ingestion of alcohol as a detonator of craving and the compulsive search behaviour of cocaine leads to a greater loss of control on use, more social problems, more risk and more antisocial behaviours. Hypothesis: the presence of a metabolite known as cocaethylene, resulting from the simultaneous use of alcohol and cocaine could explain the greater toxicity and compulsivity of these episodes. Methodology: A review was made of the scientific literature on the consequences of alcohol-cocaine interaction. Results: The alcohol-cocaine metabolic interaction increases the potential toxicity of both substances taken separately. The cocaethylene acts as a toxic per se. Its presence in the organism provokes a higher potential risk in the simultaneous consumption of alcohol and cocaine. There are more significant concentrations of cocaethylene when alcohol is administered prior to the cocaine. The results of the basic research show that a large part of the differences observed in the action of both substances, when ingested simultaneously, could be a result of modifications in the pharmacokinetics of said drugs and of the potential action of the cocaethylene, which, added to the respective actions of alcohol and cocaine, could be the basis of the increased severity observed in clinical profiles (AU)