Error-related functional connectivity of the thalamus in cocaine dependence.

Error processing is a critical component of cognitive control, an executive function that has been widely implicated in substance misuse. In previous studies we showed that error related activations of the thalamus predicted relapse to drug use in cocaine addicted individuals (Luo et al., 2013). Here, we investigated whether the error-related functional connectivity of the thalamus is altered in cocaine dependent patients (PCD, n = 54) as compared to demographically matched healthy individuals (HC, n = 54). The results of a generalized psychophysiological interaction analysis showed negative thalamic connectivity with the ventral medial prefrontal cortex (vmPFC), in the area of perigenual and subgenual anterior cingulate cortex, in HC but not PCD (p < 0.05, corrected, two-sample t test). This difference in functional connectivity was not observed for task-residual signals, suggesting that it is specific to task-related processes during cognitive control. Further, the thalamic-vmPFC connectivity is positively correlated with the amount of cocaine use in the prior month for female but not for male PCD. These findings add to recent literature and provide additional evidence for circuit-level biomarkers of cocaine dependence.

Gray matter volume correlates of global positive alcohol expectancy in non-dependent adult drinkers.

Alcohol use and misuse is known to involve structural brain changes. Numerous imaging studies have examined changes in gray matter (GM) volumes in dependent drinkers, but there is little information on whether non-dependent drinking is associated with structural changes and whether these changes are related to psychological factors-such as alcohol expectancy-that influence drinking behavior. We used voxel-based morphometry (VBM) to examine whether the global positive scale of alcohol expectancy, as measured by the Alcohol Expectancy Questionnaire-3, is associated with specific structural markers and whether such markers are associated with drinking behavior in 113 adult non-dependent drinkers (66 women). Alcohol expectancy is positively correlated with GM volume of left precentral gyrus (PCG) in men and women combined and bilateral superior frontal gyri (SFG) in women, and negatively correlated with GM volume of the right ventral putamen in men. Furthermore, mediation analyses showed that the GM volume of PCG mediate the correlation of alcohol expectancy and the average number of drinks consumed per occasion and monthly total number of drinks in the past year. When recent drinking was directly accounted for in multiple regressions, GM volume of bilateral dorsolateral prefrontal cortices correlated positively with alcohol expectancy in the combined sample. To our knowledge, these results are the first to identify the structural brain correlates of alcohol expectancy and its mediation of drinking behaviors. These findings suggest that more studies are needed to investigate increased GM volume in the frontal cortices as a neural correlate of alcohol expectancy.

Error processing and gender-shared and -specific neural predictors of relapse in cocaine dependence.

Deficits in cognitive control are implicated in cocaine dependence. Previously, combining functional magnetic resonance imaging and a stop signal task, we demonstrated altered cognitive control in cocaine-dependent individuals. However, the clinical implications of these cross-sectional findings and, in particular, whether the changes were associated with relapse to drug use, were not clear. In a prospective study, we recruited 97 treatment-seeking individuals with cocaine dependence to perform the stop signal task during functional magnetic resonance imaging and participate in follow-up assessments for 3 months, during which time cocaine use was evaluated with timeline follow back and ascertained by urine toxicology tests. Functional magnetic resonance imaging data were analysed using general linear models as implemented in Statistical Parametric Mapping 8, with the contrast 'stop error greater than stop success trials' to index error processing. Using voxelwise analysis with logistic and Cox regressions, we identified brain activations of error processing that predict relapse and time to relapse. In females, decreased error-related activations of the thalamus and dorsal anterior cingulate cortex predicted relapse and an earlier time to relapse. In males, decreased error-related activations of the dorsal anterior cingulate cortex and left insula predicted relapse and an earlier time to relapse. These regional activations were validated with data resampling and predicted relapse with an average area under the curve of 0.849 in receiver operating characteristic analyses. These findings provide direct evidence linking deficits in cognitive control to clinical outcome in a moderate-sized cohort of cocaine-dependent individuals. These results may provide a useful basis for future studies to examine how psychosocial factors interact with cognitive control to determine drug use and to evaluate the efficacy of pharmacological or behavioural treatment in remediating deficits of cognitive control in cocaine addicts.

Effects of androgen deprivation on brain function in prostate cancer patients - a prospective observational cohort analysis.

BACKGROUND: Despite a lack of consensus regarding effectiveness, androgen deprivation therapy (ADT) is a common treatment for non-metastatic, low-risk prostate cancer. To examine a particular clinical concern regarding the possible impact of ADT on cognition, the current study combined neuropsychological testing with functional magnetic resonance imaging (fMRI) to assess both brain activation during cognitive performance as well as the integrity of brain connectivity. METHODS: In a prospective observational cohort analysis of men with non-metastatic prostate cancer at a Veterans Affairs medical center, patients receiving ADT were compared with patients not receiving ADT at baseline and at 6 months. Assessments included fMRI, the N-back task (for working memory), the stop-signal task (for cognitive control), and a quality of life questionnaire. RESULTS: Among 36 patients enrolled (18 in each group), 30 completed study evaluations (15 in each group); 5 withdrew participation and 1 died. Results for the N-back task, stop-signal task, and quality of life were similar at 6 months vs. baseline in each group. In contrast, statistically significant associations were found between ADT use (vs. non use) and decreased medial prefrontal cortical activation during cognitive control, as well as decreased connectivity between the medial prefrontal cortex and other regions involved with cognitive control. CONCLUSIONS: Although ADT for 6 months did not affect selected tests of cognitive function, brain activations during cognitive control and functional brain connectivity were impaired on fMRI. The long-term clinical implications of these changes are not known and warrant future study.

Neural processes of an indirect analog of risk taking in young nondependent adult alcohol drinkers-an FMRI study of the stop signal task.

BACKGROUND: Alcohol abuse and dependence are common problems in the United States that stem from a variety of factors, one of which may be a period of high level social drinking during college and early adulthood. Extant study implicates risk taking as a cognitive factor that contributes to habitual and heavy drinking. We sought to examine the neural processes of risk taking in young, nondependent drinkers. METHODS: We compared 20 young adult social drinkers with a high level of alcohol use (AH), as defined by number of drinks per month, and 21 demographically matched drinkers with low to moderate alcohol use (ALM) in a functional magnetic resonance imaging study of the stop signal task. By contrasting risk taking (speeded) to risk aversion (slowed) trials, we examined the neural correlates of risk taking. Brain imaging data were analyzed with Statistical Parametric Mapping. Regions of interest were identified and corresponding effect sizes were examined for correlations with self-reported alcohol use. RESULTS: The results showed that, compared with ALM, AH demonstrated decreased activation in right superior frontal gyrus and left caudate nucleus when contrasting risk taking and risk aversion trials at p < 0.001, uncorrected. Furthermore, examination of the effect size data showed that the extent of these decreased regional activations correlated with frequency of drinking in women, but not men. CONCLUSIONS: These findings suggest a neural analog of nondependent, high level drinking. Specifically, high level social drinking is associated with altered activation of the caudate and superior frontal cortex, an association that appears to be stronger in women than in men and is strongly tied to the frequency of drinking. These results are relevant in understanding risk taking behavior in social drinking as well as in examining the potential path from high level social use in young adults to dangerous alcohol consumption later in life.

Deficits in default mode network activity preceding error in cocaine dependent individuals.

BACKGROUND: Cocaine dependence is associated with cognitive deficits and altered task-related cerebral activation in cognitive performance (see Li and Sinha, 2008, for a review). Relatively little is known whether these individuals are also impaired in regional brain activation of the default mode network (DMN). We demonstrated previously that greater activation of the default brain regions precedes errors in a stop signal task performed by healthy controls (SST, Li et al., 2007). We seek to determine whether individuals with cocaine dependence are impaired in DMN activity, specifically activity preceding error, as compared to the healthy people. We also examine the relation to years of cocaine use. METHODS: Individuals with cocaine dependence (CD, n=23) and demographics-matched healthy controls (HC, n=27) performed a SST that employed a tracking procedure to adjust the difficulty of stop trials and elicit errors approximately half of the time. Blood oxygenation level dependent (BOLD) signals of go trials preceding stop error as compared to those preceding stop success trials were extracted with generalized linear models using statistical parametric mapping. RESULTS: HC showed activation of bilateral precuneus and posterior cingulate cortices and ventromedial prefrontal cortex (vmPFC) preceding errors during the SST. In contrast, despite indistinguishable stop signal performance, CD did not show these error predicting activations. Furthermore, the effect size of error-preceding vmPFC activation was inversely correlated with years of cocaine use. CONCLUSIONS: These findings indicate DMN deficits and could potentially add to our understanding of the effects of chronic cocaine use on cerebral functions in cocaine dependence. Work to further clarify potential changes in functional connectivity and gray matter volume is warranted to understand the relevance of DMN to the pathology of cocaine misuse.