If a participant pressed to collect 20 on a trial meant to be a 240 trial, or tried to collect 20 or 40 on a dedicated 280 trial, the participant received the collected amount, thereby reducing the number of punished trials.fMRI data were analyzed using Analysis of Functional Neuroimages software . Single-subject data preprocessing procedures are outlined in Reske et al. . Multiple regressor analysis and individual linear contrasts were computed in 3dDeconvolve, including six motion regressors as well as baseline and linear drift. Deconvolution was performed to examine the decision contrast and outcome contrast . Voxels were resampled into 4 3 4 3 4-mm3 space, and whole-brain voxel wise normalized percentage signal change, the main dependent measure, was determined by dividing the beta coefficient for each of the predictors of interest by the beta coefficient for the baseline regressor and multiplying by 100. A Gaussian spatial filter blurred percentage signal change values, which were then normalized to Analysis of Functional Neuroimages Talairach coordinates . Individual subject values for risky decisions, safe decisions, risky win outcomes, and risky loss outcomes for each voxel included in a whole-brain mask were extracted for statistical analyses. Individual voxels meeting a p , .01 significance criterion as a result of statistical tests outlined below were evaluated further to determine whether they comprised a significant brain cluster after correction for multiple comparisons. In categorical analyses, for each voxel, a linear mixed effects model was performed in R to identify significant regions of percentage signal change between PSUs and DSUs for decision and outcome analyses separately. Group was the between-subjects variable, and subject was a random variable. Within-subject variables were decision type and outcome type . Cohen’s d was calculated to determine effect sizes. In dimensional analyses, multiple regressions were computed for each brain voxel,cannabis grow equipment with two separate dependent variables: 1) percentage signal change for risky minus safe decisions and 2) percentage signal change for risky wins minus losses. Predictors in each regression were the following: 1) baseline stimulant uses, 2) interim stimulant uses, 3) baseline marijuana uses, and 4) interim marijuana uses.
In extracting significant whole-brain clusters, neuroimaging analysis software has been criticized for underestimating spatial autocorrelation, leading to insufficient multiple com parison corrections. In response to these concerns, 1) the updated 3dFWHMx program was employed to more reliably estimate true autocorrelation and smoothness present following blurring and 2) an updated version of 3dClustSim was run to account for autocorrelation given our voxel/whole-brain mask size, 10,000 Monte Carlo simulations and two-sided thresholding with an overall voxel p statistical threshold of .01 and a corrected clusterwise alpha value of .01. Data smoothness was approximately 6 mm, and . 19 neigh boring voxels comprised a significant brain cluster.Three hypotheses were tested. First, consistent with the prediction that PSUs would exhibit riskier task performance than DSUs, PSUs more frequently made a risky decision following a win compared with DSUs, while DSUs more frequently made a safe decision following a risky win. This pattern supports previous findings that PSUs are more reactive to rewards . Second, although it was predicted that PSUs would show greater activation in reward processing striatal regions to risky wins than to risky losses when compared with DSUs, our re sults demonstrated the opposite effect, with PSUs exhibiting lower striatal BOLD signals across outcomes than DSUs. However, this finding is consistent with a longitudinal study of sensation-seeking adolescents in which striatal hypoactivation predicted future problematic drug use; the authors theorized that lower striatal activity may lead to a compensatory mechanism in which one seeks out increased risk to gain greater stimulation, thereby balancing reward center hypo activation . PSUs exhibited greater temporo-occipital BOLD signals to wins than to losses, findings consistent with a recent meta-analysis reporting that 86% of addiction-related neuroimaging studies demonstrate significant visual cortex activity to drug cues . Although the RGT did not test drug-related responses, our results demonstrate an analo gous relationship to general reward cues, suggesting that PSUs may allocate greater visual attention to risky rewards than to risky losses. Middle temporal lobe is involved in memory of reward-based information critical for future oriented decision making, suggesting that PSUs may be less able to consolidate information about outcomes differ ently . Together, PSUs are characterized by visual attention and memory activation during risky rewards but blunted responsivity to loss outcomes. Our third prediction was supported in that PSUs exhibited lower PFC, insula, and cingulate BOLD signals than DSUsduring risky feedback. These findings align with a recent study conducted by our research group demonstrating that during a task evaluating how individuals learn to make decisions, PSUs exhibited lower insula and ACC activation across all available outcomes than DSUs .
Such pat terns are consistent with previous reports of PFC, insula, and ACC attenuations in chronic stimulant users that are linked with decreased ability to adapt behavior using prior experiences/ reduced inhibitory control, interoceptive awareness, and conflict monitoring, respectively . Thus, young adults pre disposed to SUD may have prior deficits in recruiting neural effort toward critical decision-making processes. Nonhypothesized group differences also emerged in thalamic, precuneus, and posterior cingulate regions that warrant discussion. PSUs showed relatively greater pre cuneus and posterior cingulate BOLD signals when making risky decisions than when making safe decisions when compared with DSUs. Such differences are consistent with previous findings in SUD samples that heightened activation of these areas during exteroceptive awareness may underlie the maintenance and exacerbation of substance use . Greater thalamic response to risky reward versus loss feedback in PSUs is consistent with research demon strating that thalamic BOLD signals are linked to relapse in cocaine-dependent individuals . Thalamus acts as a relay center for the brain by sending sensory information to insula for further interoceptive processing ; hypo activation to loss may reflect differences in relay and integration of information during decision making. With respect to baseline characteristics, DSUs endorsed higher baseline levels of state depression than PSUs, which may have affected RGT performance given that individuals with depression tend to be risk averse . However, given that mean scores for DSUs are substantially below the Beck Depression Inventory threshold for clinical depression [in nonclinical populations, scores above 20 indicate depression ; it is unlikely that DSUs performed in a manner consistent with samples with depression].Across OSUs, lower frontal, temporal, parietal, insular,cannabis grow table and thalamic BOLD signals during risky decisions compared with safe decisions predicted greater future marijuana use . These regions are considered important for executive functions such as inhibitory control, working memory, and attention as well as for being relay centers for integrating information critical for decision making . Therefore, blunted responses in these regions while making choices between risky and safe optionsdose–response effect may exist between brain activation and marijuana use, the relationship between brain activation and stimulant use may be better defined through a categorical perspective that includes accompanying clinical symptomology. Although PSUs and DSUs used marijuana at significantly high rates , groups did not differ categorically in marijuana abuse/dependence frequency. In contrast, stimulant use in and of itself might not be related to brain differences unless it is accompanied by clinical problems, suggesting that a categorical perspective is a more useful way to conceptualize differences.
Cambodia has the highest HIV prevalence of any Asian country, and over the last decade has experienced the most serious HIV/AIDS epidemic in Southeast Asia. Heterosexual contact is the major route of HIV trans mission, and female sex workers remain the group at highest risk. Although crucial progress has been made in reducing risky sexual behavior, including widespread condom use and promotion of reduced number of sexual partners, HIV prevalence among FSW remains high, ranging from 11% to 26%. Poverty, low literacy, a high prevalence of sexually transmitted infections, and a highly mobile work force are contributing factors to the epidemic. Recent research has also identified drug use and, in particular, amphetamine-type stimulant use as a serious emerging problem associated with HIV risk among FSW, which threatens to reverse downward trends in HIV infection rates in the region. Amphetamine-type stimulants include a range of syn thetic psychostimulants, including methamphetamine, amphetamine, and ecstasy, which can be injected, smoked, or taken orally. Effects of these drugs include euphoria, alertness, arousal, increased libido, increased sympathetic nervous responses, , and perceived increases in confidence, energy and physical strength. In Cambodia, a pill form of methamphetamine known as “yama” is widely produced, trafficked, and used. The tablets gener ally contain about 25% methamphetamine. “Crystal” is generally about 85% metham phetamine and more addictive. Although yama pills aresw allowed, both forms are usually melted and the vapors inhaled, resulting in rapid neurologic effects. Use of ATS has been associated with elevated HIV risk behavior in many countries and in several population sub groups. The United Nations Office on Drugs and Crime reports that use of these drugs is widespread in Asia and increasing rapidly in Cambodia. In Cambodia, ATS are highly available both in pill and crystalline form and are generally ingested or smoked; injection use is uncommon. The Cambodia National Authority for Combating Drug Abuse estimated that 70% of all drug users in Cambodia use ATS. The drug accounts for the majority of all drug seizures by authorities, and, in pill form, has been ranked as the leading drug of abuse for the past nine years with consistent increases since 2006, at which time it was estimated that 30,000 tablets of yama were consumed orally or smoked there daily. Use is particularly high among vulnerable populations, including FSW,men who have sex with men , and street children.Self-reported measures of drug use have the advantage of being noninvasive and permit evaluation over longer time periods compared with bio chemical assessments. However, study participants may misrepresent drug use due to social desirability bias, stigma, poor recall, poorly worded questions, or poorly worded response categories in surveys and interviews, all of which could result in mis-classification of measured exposures. Although studies have shown that the use of Audio Computer-Assisted Self Interview increases reporting of sensitive and stigmatized behaviors, research suggests that the validity of self-reported drug use varies by population, race/ ethnicity, mental health, and drug treatment status, although not by gender. Accuracy has varied in studies of arrestee populations but have been reported as higher in groups sampled in emergency department and STI clinics. Those that report more frequent drug use, compared to infrequent use, are more likely to self-report recent drug use. Urine toxicology assessments provide sensitive and valid measures of many drug types; but some, like ATS, are restricted to a short time frame due to rapid metabolization. The detection window may also depend on the physical condition of the individual , route of drug ingestion , frequency of use, and drug-related factors such as purity. To explore the validity of self-reported ATS use among young FSW in Phnom Penh, Cambodia, we com pared self-reported ATS use with results from concur rently collected urine toxicology tests. We also examine whether sociodemographic, sex-work venue, and HIV status were associated with validity of self-reported ATS use.Young women at high risk of HIV infection were the target study population. Inclusion criteria were age 15–29 years, understanding of spoken Khmer, Cambodian ethnicity, reporting of at least two different sexual partners in the last month or engaging in transactional sex within the last three months, plans to stay in the Phnom Penh area for 12 months, being biologically female, and being able to provide voluntary informed consent. Study methods have been described previously. In brief, trained field assistants from the CWDA recruited women from community locations, provided study information, and obtained group informed consent. Women who consented were then seen by appointment at the YWHS-2 clinic site; free transportation was provided. Participants received US $5 and condoms at each study visit. Contact information was collected to facilitate participant tracking and maximize follow-up. Women were asked to enroll for a one-year study with quarterly study visits.All study visits included administration of a structured questionnaire in Khmer by trained inter viewers who queried participants about sociodemo graphic characteristics, health care, occupational and sexual risk exposures, alcohol and self-reported ATS use as well as testing for HIV and ATS using blood and urine samples, respectively.