As such, the present study may have been under powered to detect small effects sizes, which may account for the null findings regarding intervention effects on drinking outcomes. Future studies are encouraged to recruit larger samples of non-treatment seeking participants to better detect small effects. Furthermore, this finding should be considered in light of the sample, which was comprised of non-treatment seekers from the community, which is not the typical sample evaluated in brief intervention research. However, non-treatment seeking individuals with similar alcohol use characteristics are open to participating in brief interventions . Also of note the drinking outcomes in this study were evaluated using variables derived from the TLFB as the primary outcome measure. There is some evidence that some individuals under-report substance use when the TLFB is administered by an interviewer rather than a computer , potentially due to a social desirability bias in which participants wish to appear favorably to the interviewer. In the present study, the TLFB assessment was conducted by a trained research assistant and not the clinician who delivered the brief intervention in order to reduce this bias. However, the TLFB is a retrospective self-report measure and as such is subject to limitations including inaccuracies in participant recall. In light of the null findings regarding intervention effects on drinking in this study, it is perhaps not surprising that intervention condition was not associated with differences in neural cue reactivity in this sample. While it has been argued that neuroimaging techniques may be sensitive to mechanisms of behavior change , in the present study,grow bench neural processing of alcohol taste cues was no more sensitive to intervention effects than traditional measures of drinking outcomes.
It should be noted however, that the alcohol taste cues task used in this study was abbreviated from its original version in order to increase the number of trials without substantially increasing scan duration. Additionally, the current version of the task used water as a control condition, while the original version employed an appetitive control condition in the form of litchi juice. While the present version was recently validated in a separate sample , it may not have recruited the reward circuitry in response to alcohol cues as robustly as its previous iteration. Importantly, it should be noted that across both conditions, exposure to alcohol taste resulted in increased activation in frontal and limbic regions, compared to water taste, suggesting the task was fundamentally internally valid. Nevertheless, the magnitude of the activation may have been more limited due to the combination of the shortened trial duration and use of a non-appetitive control thus hindering efforts to detect intervention effects on neural processing of alcohol cues. Considered together, both factors likely posed significant challenges to the primary aims of the study, which fundamentally represented an interaction effect between treatment type and cue type. Given this, large magnitude main effects for both experimental factor would be optimal to bring the interaction into sharpest relief. Thus, the relatively modest effect size of the intervention and the sufficient but potentially smaller effects in the neuroimaging paradigm constrained the experimental tests. Future studies using neuroimaging to understanding brief interventions will require at least substantially larger sample sizes for a detectable clinical effect and potentially different neuroimaging paradigms. Regarding the prediction of drinking outcomes, the most compelling finding in the present study is that activation to alcohol tastes in the precuneus and medial frontal gyrus was negatively associated with percent heavy drinking days.
The effect was such that individuals who had greater neural reactivity to alcohol taste in the precuneus and prefrontal cortex had fewer percent heavy drinking days in four weeks following the fMRI scan. Likewise, across groups, activation to alcohol tastes in the precuneus was negatively associated with average drinks per week. This pattern of results suggests that greater activation of the precuneus and frontal cortex during neural processing of alcohol taste cues, compared to control cues, predicts less drinking in the subsequent month. This effect was found across conditions, control and experimental, and is generally consistent with previous work suggesting that the precuneus is sensitive to changes in cuereactivity and possibly to changes in addiction severity . The precuneus has also been implicated in a meta-analytic review of functional neuroimaging studies of alcohol cue reactivity . Thus the implication of precuneus activation as a predictor of subsequent drinking in the real world extends this line of research and suggests that this region may serve as an intervention target, particularly with regard to the salience of alcohol cues. Although the vast majority of neuromodulation studies to address motivation in addiction have focused on the frontal lobes , and dorsolateral prefrontal cortex in particular, recent investigations have shifted attention to the precuneus , with some success. This prospect is particularly exciting in the context of psychological interventions. The precuneus has been functionally implicated in self-related cognition , which in many cases is essential for behavioral interventions to have an impact. For example, in the context of a brief intervention, a person must encode the factual information provided and square it with their own self perceptions.
Furthermore, in the current study’s intervention, participants were specifically asked what they wanted to do next and this necessarily demands meaningful self-related cognitive processing to generate behavior change. To illustrate this by contrast, we would have no expectation that a brief intervention would have a meaningful impact for a hypothetical individual who had no capacity to think abstractly about him or herself . Thus, self-related cognition is a necessary elementary information processing capacity for this type of intervention to be useful and the current study suggests that the extent to which this was engaged was associated with a more favorable outcome. Of course, this interpretation requires considerable caution because it is inherently conjecture and the precuneus has been implicated in a number of other cognitive functions. A recent review of psychosocial interventions for addiction medicine identified increased recruitment of self-referential processing regions, including the precuneus and medial prefrontal cortex,plant nursery benches in response to targeted motivational interventions . Additionally, in cannabis users, greater precuneus activation during a motivational interviewing intervention was associated with a reduction in cannabis problems at follow-up ; further indicating that activation of self-referential processing circuitry may be important for treatment response. Other psychological interventions, including cue-extinction and episodic future thinking training, may be successful at increasing self-related cognition through precuneus activation. Precuneus activation has been demonstrated in cigarette smokers who were told to engage in self-focused coping during a cue-exposure task , indicating the interventions targeting self-focused coping during exposure to drug cues may effectively activate this brain region. Exposure to episodic future thinking activates the precuneus and mPFC and results in alcohol dependent individuals increasing their valuation of future monetary rewards while lowering demand intensity for alcohol rewards . Frontoparietal circuitry, including the precuneus, is activated when participants make voluntary choices to cognitively reappraise craving responses or freely view craving cues . Of note, the precuneus is not neuroanatomically uniform, with distinct functional sub-regions according to both the anterior-posterior and dorsal-ventral axes, and distinct patterns of functional connectivity by sub-region . The current study reveals associations for the precuneus in general, but cannot speak to sub-regional activation. In sum, the current study sought to examine whether a brief intervention would reduce both drinking and alcohol motivation as measured by neural reactivity to alcohol cues and neither hypothesis was supported. This conclusion, however, must be tempered by effect size considerations for both the intervention and the paradigm, as well as the apparently substantial reactivity effects present in the control condition. Each of these has important methodological implications for future studies of the neural mechanisms of alcohol-related behavior change. In addition, independent of intervention, exploratory analyses revealed differential neural reactivity that predicted more favorable outcomes, particularly in the precuneus, suggesting that is a promising neural substrate warranting further study in this line of inquiry.
Liver disease is a leading cause of morbidity and mortality in human immunodeficiency virus –infected persons. Coinfection with hepatitis C virus is commonly implicated and has been associated with accelerated progression of liver fibrosis and cirrhosis compared with HCV infection alone. Some studies show that HIV-monoinfected adults have greater liver fibrosis than those with neither HIV nor HCV infection. Possible reasons for the reported increase in liver fi- brosis in HIV-monoinfected adults include both immunosuppression and uncontrolled HIV viral replication, factors that have been associated with fibrosis in studies of predominantly HIV-monoinfected patients. Perturbations in fat and metabolic parameters, including increased adiposity, insulin resistance, diabetes, and dyslipidemia, have also been postulated as possible causes of fibrosis in the HIV setting, but few studies have examined these factors. Furthermore, the few studies that have examined the association of HIV infection with fibrosis have used indirect serummarkers, such as liver enzyme elevations or indirect markers of liver fibrosis. Although liver biopsy remains the clinical reference standard to assess fibrosis, it is generally not clinically indicated in HIV-infected persons. Transient elastography is an alternative, noninvasive imaging technique that can directly visualize the liver to estimate the degree of fibrosis. In the current study, we examined the association of HIV, HCV, fat and metabolic parameters with liver fibrosis estimated using ultrasound-based TE in a geographically and ethnically diverse cohort of US women with HIV monoinfection, HCV infection , or neither infection from the Women’s Interagency HIV Study . We hypothesized that both HCV and HIV infection would be associated with increased fibrosis compared with the absence of both infections and that metabolic perturbations would be independently associated with fibrosis in these groups.The following primary predictors and covariates of liver stiffness were included in the analyses: HIV infection ; chronic HCV infection ; demographic factors ; menopausal status; lifestyle factors, including history of injection drug use, alcohol use ; marijuana use , smoking ; body composition, including waist circumference, waist-to-hip ratio, and BMI ; and metabolic factors, including diabetes mellitus , insulin resistance estimate dusing the homeostasis model assessment, fasting lipid levels , use of lipid-lowering therapy, and use of antidiabetes medications. In analyses among HIV-infected women, current CD4, nadir CD4, current HIV RNA, history of clinical AIDS, and current use of highly active ART and ART by class were assessed. In analyses among HCV-infected women, HCV RNA level and HCV genotype were also assessed. In exploratory analyses, we controlled for liver enzyme levels . Multiple imputation with the Markov chain Monte Carlo method was used to impute missing covariates.We compared demographic and clinical characteristics among 4 groups: women with HIV monoinfection, HIV/HCV coinfection, HCV monoinfection, or neither infection; we used the Kruskal-Wallis test for continuous variables and Fisher’s exact test for categorical variables. We used multi-variable linear regression with robust standard errors to evaluate the association of HIV and HCV infection and metabolic parameters with liver stiffness. Liver stiffness was found to be right skewed and was therefore log-transformed for analysis; results were back-transformed to produce estimated percentage differences. We used relative risk regression with a robust variance estimator to investigate the association of HIV and HCV status with significant fibrosis. To determine whether HIV and HCV infection were independently associated with liver stiffness, multi-variable models were sequentially adjusted for demographics, lifestyle factors, and metabolic parameters. Factors forced in the full model included age and race or ethnicity. We then constructed separate models in participants with HIV infection alone, HIV/ HCV coinfection and HCV monoinfection, and neither infection, to examine the associations of demographic, lifestyle, and metabolic risk factors with liver stiffness within each group. HIV-related factors were included in models of HIV-infected women, and HCV-related factors in models of HCV-infected women. Stepwise regression with a cutoff at P ≤ .05 was used for entry and retention; the candidate variables were selected based on their hypothesized associations with fibrosis. We used Bayesian model averaging as an alternative model building approach; predictors with posterior probabilities >35% were retained in the model . Models constructed using the 2 approaches were very similar. Bayesian model averaging was performed using the BMA package for the R statistical computing language . All analyses were conducted using the SAS system, version 9.2 .The demographic, behavioral and clinical characteristics of the 314 women included in the analysis are shown in Table 1, stratified by HIV and HCV status.