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Official websites use. Share sensitive information only on official, secure websites. E-mail: egarza imp. The striatum and thalamus are subcortical structures intimately involved in addiction. The morphology and microstructure of these have been studied in murine models of cocaine addiction CA , showing an effect of drug use, but also chronological age in morphology. Human studies using non-invasive magnetic resonance imaging MRI have shown inconsistencies in volume changes, and have also shown an age effect. In this exploratory study, we used MRI-based volumetric and novel shape analysis, as well as a novel fast diffusion kurtosis imaging sequence to study the morphology and microstructure of striatum and thalamus in crack CA compared to matched healthy controls HCs , while investigating the effect of age and years of cocaine consumption. We did not find significant differences in volume and mean kurtosis MKT between groups. However, we found significant contraction of nucleus accumbens in CA compared to HCs. We also found significant age-related changes in volume and MKT of CA in striatum and thalamus that are different to those seen in normal aging. Interestingly, we found different effects and contributions of age and years of consumption in volume, displacement and MKT changes, suggesting that each measure provides different but complementing information about morphological brain changes, and that not all changes are related to the toxicity or the addiction to the drug. Our findings suggest that the use of finer methods and sequences provides complementing information about morphological and microstructural changes in CA, and that brain alterations in CA are related cocaine use and age differently. The striatum and thalamus are subcortical structures greatly affected in the physiopathology of cocaine addiction in animal models and possibly in humans. However, non-invasive neuroimaging studies in human cocaine addicts CAs have shown inconsistent and conflicting neuroanatomical abnormalities in striatum and thalamus. A number of studies have observed lower volume in striatum, 6 , 7 larger striatal and thalamic volumes, 8 , 9 , 10 reduced volume in anterior and increase in posterior striatum, 11 or no volumetric differences whatsoever. Compared to inhaled cocaine, crack cocaine smoked is clinically related to stronger craving, addiction and deterioration in cognition. To better understand the neuroanatomical effects of cocaine as the main drug of use and the mechanism of addiction, there is a need for large-scale studies using more sophisticated computational neuroanatomical methods and novel neuroimaging sequences in human addicts, while focusing on one type of cocaine delivery separately. Also, it would be important to study brain morphology in a wider range of ages young and older addicts , as it has been shown that brain changes related to cocaine abuse tend to worsen with age in young mice 3 and in humans. Volumetric and shape analyses are performed based on high-resolution T1-weighted magnetic resonance imaging data. Shape analysis refers to the study of the three-dimensional shape of the subcortical nuclei using the information of the automatic segmentation and shape-based models. These metrics, surface area and displacement, are related to biological processes and pathology for example, schizophrenia , and provide different and complementary information than volume. Diffusion kurtosis imaging DKI is a novel imaging technique known to be very sensitive to tissue microstructure, even in regions of crossing fibers. However, it has not been used for the study of substance abuse and addiction. The basis of DKI is that in tissue, microstructural components hinder free that is, Gaussian diffusion of water. DKI, however, may or may not be related to macrostructural volume or shape changes measured with T1-weighted images, as DKI measures microstructural changes. One typically reported DKI metric is the mean kurtosis MKT , which has been associated with microstructural changes in a host of diseases such as stroke, 24 but has also been shown to be sensitive to more subtle brain alterations as in mild traumatic brain injury, 25 , 26 mild chronic stress 27 and even the brain remodeling that is part of normal aging. Education was matched as closely as possible. The recruitment criteria are shown in Supplementary Table 1. The study was carried out according to the Declaration of Helsinki. All participants were invited through posters placed in several centers for addiction treatment. HCs were recruited from the Institute that is, administrative workers and using fliers around the city. Participants had the study fully explained to them and provided verbal and written informed consent. The participants underwent clinical and cognitive tests besides the MRI as part of the main ongoing addiction project see Supplementary Methods and Results and Supplementary Table 2 for details , which are not part of this study. Tobacco use in this population is unavoidable; therefore, we determined years of tobacco use and tobacco dependency in CAs and HCs see Supplementary Methods and Results. Psychiatric comorbidities, lifetime medication and polysubstance use are reported in Supplementary Table 3 , respectably. The clinical and MRI sessions were done the same day as minimum and 4 days apart as maximum. We acquired structural T1-weighted data and DKI data using the fast kurtosis acquisition scheme. Specifically, the fast kurtosis protocol from Hansen et al. We obtained segmentations and volumetric measures for whole striatum and thalamus, as well as their subdivisions. For shape analysis, indices of surface displacement 20 , 40 and surface area 41 for the striatum and thalamus were derived. Briefly, surface displacements were derived based on the average of the nonlinear portions of the 21 transformations estimated using MAGeT-Brain as the dot product between the surface normal and the local nonlinear registration vector at each point. Native surface area was estimated using a median surface representation based on the 21 surfaces from the MAGeT-Brain pipeline in native space. Surface area was estimated by assigning one-third of the surface area of each triangle to each vertex within the triangle. Tensor-based MKT was calculated as previously described in Hansen et al. MKT was calculated on unsmoothed data, as we aimed for region of interest-based statistics it should be noted that motion and eddy current corrections introduce slight blurring due to resampling. T1-weighted images were skull-stripped 43 and linearly co-registered to the MKT images. All variables were tested for normality using the Shapiro—Wilks test. Finally, we performed a linear regression of the right pulvinar volume and years consuming cocaine, with total brain volume, age and sex as covariates. A liberal FDR threshold was chosen due to the small sample size, the high variability of results in previous studies and consistency with previous reports on shape analysis. We superimposed the striatum and thalamus subdivision atlases to label the subnuclei location of the significant clusters. Finally, we created plots using the values of surface area and displacement observed in the peak vertex of significant clusters. Participant data are shown in Supplementary Table 1. There were no significant relationships between the morphological data and years of tobacco use in our data see Supplementary Methods and Results for details on the analysis. The interaction shows that striatum and caudate volume increased with age in the CA group and decreased in the HC group Figure 1. Scatter plot of left and right striatum corrected volume with regression lines and shadowed confidence intervals at 0. B, standard error; Stria, whole striatum; Thal, whole thalamus; vol, volume. Volume is in mm 3. The post hoc correlations with the subnuclei found no correlation with years consuming cocaine in the striatum. The multiple regression analysis confirmed this relationship Supplementary Table 7. Thus, the longer years of crack cocaine consumption the smaller right pulvinar volume. In general, the CA group had more contraction or inward displacement than the HC group in the cluster peak. The multiple regression analysis of the cluster peak showed an influence solely by age Table 2 ; Supplementary Table 8. There were no significant clusters in the thalamus. The surface area did not show significant clusters in striatum and thalamus. Striatum displacement. Negative values represent contraction; positive values represent expansion. The demographics of the fDKI smaller sample size were similar to the volume analysis. The fDKI analysis did not show a group effect. Mostly in the thalamus, MKT decreased with age in CAs, whereas it increased in HCs, although it did show a different pattern in striatum. Scatter plot of top striatum MKT and bottom thalamus MKT with regression lines and shadowed confidence intervals at 0. Striatum MKT showed no significant correlations. The multiple regression analysis with age as covariate maintained the significant correlation in left thalamus MKT Table 2 ; Supplementary Table 9. We did not find significant correlations between striatum and thalamus MKT and volume. Our findings suggest that morphometric changes in active crack cocaine addiction are subtle, and that volumetric analysis is less sensitive than shape analysis and DKI to measure these changes. However, we also found that volume and shape in the striatum were more related to abnormal aging in CAs, whereas morphometric differences in thalamus and DKI differences in both striatum and thalamus were more related to years consuming the drug. In our sample, striatum and thalamus volumes were not different between HCs and crack CAs. This agrees with the study by Martinez et al. In their study, they also admitted patients with active crack cocaine addiction and had a smaller sample size than ours. Narayana et al. In studies that include the thalamus, polysubstance users had greater volume in the right thalamus compared to cocaine users, and another study found that cocaine-dependent subjects have decreased volume in the left thalamus compared to HCs. In our case, the HCs were closely paired for age, sex, handedness and education. We found that striatum volume increased with age in our CA group, and the effect was more prominent in the left postcommissural caudate. In healthy human population, striatum and thalamus volumes decrease with normal aging, suggesting age-related atrophy in our sample. Gray matter volume decrease shown by MRI is related to a decrease in synaptic spine density in murine models. Instead, it could also suggest reorganization in circuitry, scarring or inflammation. However, we found a positive medium—high correlation between years of consumption and age, which suggests that these variables are difficult to differentiate and this complicates interpretation. Thalamus volume was not affected by age in the CA group as in striatum. A deeper investigation showed that longer years consuming crack cocaine were associated with decreased right pulvinar volume. Age did not affect the statistical model; therefore, we suspect the effect may be more related to years of consumption. The pulvinar is a thalamic nucleus highly connected to the visual cortex and the superior colliculus, and recent studies suggest one of its main functions is visual attention and modulation. The shape analysis showed significant changes in striatum anatomy between the groups, as opposed to volume. The NAcc seems to be involved in the intoxication and withdrawal stages of cocaine addiction, with the consequent drug-seeking behavior. A murine model of adolescent cocaine exposure determined displacement differences in striatum, with significant expansion of the lateral surface and contraction of the medial surface after 30 days of abstinence. This is similar to the findings in volume. This evidence may suggest that, although the NAcc is contracted in crack cocaine addiction, there is a tendency to expand with age. Similarly to volume, this could be related to either an increase of dendritic spines or gliosis. To our knowledge, this is the first shape analysis study in cocaine-addicted humans; therefore, bigger sample sizes and longitudinal studies are needed to corroborate these results. It did show an age-related group interaction in striatum and thalamus with low effect sizes. Falangola et al. For gray matter, the MKT was seen to continue to increase through life, whereas for white matter MKT was found to increase rapidly up to age 18 and then steadily decline. In agreement with that study, MKT increased with age in the HC group, but decreased with aging in the CA group, especially evident in thalamus. Interestingly, introducing years of consumption negatively affected the model, and we found significant correlation between thalamic MKT and years of consumption. This may suggest that MKT may reflect both substance-related and age-related alterations, with a higher specificity for the former. A decreased MKT compared to normal brain tissue would suggest a less complex tissue microstructure with fewer diffusion barriers causing the diffusion process to be less non-Gaussian. Specific causes for this could be loss of neurites, leading to fewer cell connections, decreased tissue integrity and increased extracellular space. This may be corroborated by the significant negative correlations with years of cocaine use that, when compared with the pulvinar volume correlation, could suggest a reflection of thalamic atrophy. To our knowledge, this is the first study to use DKI in substance addiction, hence more studies are needed in this and other types of substance abuse. There were several limitations to our study. With the low effect sizes in all the morphological contrasts, it seems that higher sample sizes may be needed to find more significant differences in these areas. Nevertheless, we were able to obtain significant results with our limited sample sizes. The DKI analysis had the lowest sample size, and still it showed a similar effect size than the other analyses. And, unlike the rest of the analyses, the DKI showed thalamic effects as well as striatal. However, this approach was preferred to allow for a more exploratory study and we have successfully used it in our previous studies. Tobacco use and dependency was prevalent in half of our CA group, and although we did not find any effects in striatum and thalamus, one study has shown striatal volume and shape relation to craving tobacco. Studies in murine models may help to model the nature of the effects of polysubstance abuse, age and years of consumption. Our findings show morphological and microstructural changes in crack CAs, related to age and years of cocaine consumption. Most importantly, we found that striatal morphological changes may be more related to age, whereas thalamic changes may be more related to years consuming. We also found abnormal MKT development with age and years of consumption, highlighting the potential for MKT, and DKI in general, as a method for in vivo investigation of the effects of addiction on brain microstructure. The shape analysis showed contraction of the NAcc when compared to HCs. We thank the people who helped this project in one way or another: Francisco J. Finally, we thank the study participants for their cooperation and patience. This section collects any data citations, data availability statements, or supplementary materials included in this article. As a library, NLM provides access to scientific literature. Transl Psychiatry. Find articles by E A Garza-Villarreal. Find articles by MM Chakravarty. Find articles by B Hansen. Find articles by S F Eskildsen. Find articles by G A Devenyi. Find articles by D Castillo-Padilla. Find articles by T Balducci. Find articles by E Reyes-Zamorano. Find articles by S N Jespersen. Find articles by P Perez-Palacios. Find articles by R Patel. Find articles by J J Gonzalez-Olvera. Volume mean, s. Open in a new tab. Click here for additional data file. Similar articles. Add to Collections. Create a new collection. Add to an existing collection. Choose a collection Unable to load your collection due to an error Please try again. Add Cancel.
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How can I buy cocaine online in Mandeville
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