Marisa M. Silveri

Performance on the Stroop predicts treatment compliance in cocaine-dependent individuals

Treatment dropout is a problem of great prevalence and stands as an obstacle to recovery in cocaine-dependent (CD) individuals. Treatment attrition in CD individuals may result from impairments in cognitive control, which can be reliably measured by the Stroop color–word interference task. The present analyses contrasted baseline performance on the color-naming, word-reading, and interference subtests of the Stroop task in CD subjects who completed a cocaine treatment trial (completers: N=50) and those who dropped out of the trial before completion (non-completers: N=24). A logistic regression analysis was used to predict trial completion using three models with the following variables: the Stroop task subscale scores (Stroop model); the Hamilton depression rating scale (HDRS) scores (HDRS model); and both the Stroop task subscale scores and HDRS scores (Stroop and HDRS model). Each model was able to significantly predict group membership (completers vs non-completers) better than a model based on a simple constant (HDRS model p=0.02, Stroop model p=0.006, and Stroop and HDRS model p=0.003). Models using the Stroop preformed better than the HDRS model. These findings suggest that the Stroop task can be used to identify cocaine-dependent subjects at risk for treatment dropout. The Stroop task is a widely available, reliable, and valid instrument that can be easily employed to identify and tailor interventions of at risk individuals in the hope of improving treatment compliance.

Ontogeny of ethanol elimination and ethanol-induced hypothermia

Ontogeny of ethanol elimination rates and ethanol-induced hypothermia were examined as possible mechanisms contributing to the marked reduction in ethanol sensitivity early in life (Little et al., 1996; Silveri & Spear, 1998) and the notable gender difference in ethanol sleep-time seen in adult animals (Silveri & Spear, 1998). Elimination rates and brain/blood ethanol levels were determined following doses of 1.5 or 4.5 g/kg ethanol in male and female Sprague-Dawley rats at postnatal days (P)16, 26, 36, or 56. Animals were sacrificed at 40, 80, or 160 min post-injection, with ethanol elimination rates estimated from the slope of the regression of blood and brain alcohol levels across the three sampling periods. P16 animals exhibited the slowest rate of ethanol metabolism, while no gender effects were evident at any age. Observed ontogenetic increases in ethanol hypothermia were not systematically related to the ontogeny of ethanol metabolism. Factors other than ontogenetic changes in ethanol metabolism, hypothermia, or the distribution of ethanol between brain and blood must underlie the relative insensitivity to ethanol often reported in young and adolescent organisms, a fruitful area for future studies given the frequent use and misuse of alcohol by human adolescents.

Prefrontal and temporal gray matter density decreases in opiate dependence

RationaleThere have been only a few structural brain-imaging studies, with varied findings, of opiate-dependent subjects. Voxel-based morphometry (VBM) is suitable for studying whole brain-wise structural brain changes in opiate-dependent subjects.ObjectivesThe objective of the current study is to explore gray matter density in opiate-dependent subjects.MethodsGray matter density in 63 opiate-dependent subjects and 46 age- and sex-matched healthy comparison subjects was compared using VBM.ResultsRelative to healthy comparison subjects, opiate-dependent subjects exhibited decreased gray matter density in bilateral prefrontal cortex [Brodmann areas (BA) 8, 9, 10, 11, and 47], bilateral insula (BA 13), bilateral superior temporal cortex (BA 21 and 38), left fusiform cortex (BA 37), and right uncus (BA 28).ConclusionsThis study reports that opiate-dependent subjects have gray matter density decreases in prefrontal and temporal cortex, which may be associated with behavioral and neuropsychological dysfunction in opiate-dependent subjects.

Neuropsychological Consequences of Opiate Use

Approximately 3.7 million individuals have used heroin and other opiate substances in their lifetime. Despite increasing knowledge of the effects of heroin, it remains the most abused opiate and use among adults has recently increased. The empirical literature examining the neurocognitive effects of acute and chronic opioid use remains limited; however, findings to date suggest that the use of opiates has both acute and long-term effects on cognitive performance. Neuropsychological data indicate deficits in attention, concentration, recall, visuospatial skills and psychomotor speed with both acute and chronic opioid use. The long-term effects of opiate use appear to have the greatest impact on executive functions, including the ability to shift cognitive set and inhibit inappropriate response tendencies. Factors that contribute to addiction and recovery are also discussed, as it is difficult to disentangle the effects of opiate use on cognitive performance from other factors that may affect neurobehavioral measures.

Why so impulsive? White matter alterations are associated with impulsivity in chronic marijuana smokers.

Difficulty monitoring and inhibiting impulsive behaviors has been reported in marijuana (MJ) smokers; neuroimaging studies, which examined frontal systems in chronic MJ smokers, have reported alterations during inhibitory tasks. Diffusion tensor imaging (DTI) provides a quantitative estimate of white matter integrity at the microstructural level. We applied DTI, clinical ratings, and impulsivity measures to explore the hypotheses that chronic, heavy MJ smokers would demonstrate alterations in white matter microstructure and a different association between white matter measures and impulsivity relative to nonsmoking control subjects (NS). Fractional anisotropy (FA), a measure of directional coherence, and trace, a measure of overall diffusivity, were calculated for 6 locations including bilateral frontal regions in 15 chronic MJ smokers and 15 NS. Subjects completed clinical rating scales, including the Barratt Impulsivity Scale (BIS). Analyses revealed significant reductions in left frontal FA in MJ smokers relative to NS and significantly higher levels of trace in the right genu. MJ smokers also had significantly higher BIS total and motor subscale scores relative to NS, which were positively correlated with left frontal FA values. Finally, age of onset of MJ use was positively correlated with frontal FA values and inversely related to trace. These data represent the first report of significant alterations in frontal white matter tracts associated with measures of impulsivity in chronic MJ smokers. Early MJ use may result in reduced FA and increased diffusivity, which may be associated with increased impulsivity, and ultimately contribute to the initiation of MJ use or the inability to discontinue use.

Adolescents at risk for alcohol abuse demonstrate altered frontal lobe activation during Stroop performance.

BACKGROUND Children and adolescents, family history positive (FH+) for alcoholism, exhibit differences in brain structure and functional activation when compared to family history negative (FH-) counterparts. Given that frontal brain regions, and associated reciprocal connections with limbic structures, undergo the most dramatic maturational changes during adolescence, the objective of this study was to compare functional brain activation during a frontally mediated test of response inhibition in 32 adolescents separated into low-risk (FH-) and high-risk (FH+) groups. METHODS Functional magnetic resonance (fMRI) blood oxygen level-dependent data were acquired at 1.5 Tesla during performance of Stroop Color Naming, Word Reading, and Interference. Preprocessing and statistical analyses, covaried for age, were conducted in SPM99 using a search territory that included superior, middle, and inferior frontal gyri (trigone region), anterior cingulate gyrus (CG), and left and right amygdala. RESULTS Significantly greater activation in the fronto-limbic search territory was observed in FH+ relative to FH- subjects during Stroop Interference. In addition, a significant regression between brain activation and family history density was observed, with a greater density being associated with increased activation in regions including middle frontal gyrus (BA9) and CG (BA24). CONCLUSIONS These data demonstrate a significant influence of FH status on brain activation during the performance of a response inhibition task, perhaps reflecting a neurobiological vulnerability associated with FH status that may include reduced neuronal efficiency and/or recruitment of additional neuronal resources. These findings are important given that the adolescent developmental period is already associated with reduced inhibitory capacity, even prior to the onset of alcohol use.

Frontal lobe γ-aminobutyric acid levels during adolescence: associations with impulsivity and response inhibition.

BACKGROUND The brain undergoes major remodeling during adolescence, resulting in improved cognitive control and decision-making and reduced impulsivity, components of behavior mediated in part by the maturing frontal lobe. γ-Aminobutyric acid (GABA), the main inhibitory neurotransmitter system, also matures during adolescence, with frontal lobe GABA receptors reaching adult levels late in adolescence. Thus, the objective of this study was to characterize in vivo developmental differences in brain GABA levels. METHODS Proton magnetic resonance spectroscopy was used at 4 T to acquire metabolite data from the anterior cingulate cortex (ACC) and the parieto-occipital cortex (POC) in adolescents (n=30) and emerging adults (n = 20). RESULTS ACC GABA/creatine (Cr) levels were significantly lower in adolescents relative to emerging adults, whereas no age differences were observed in the POC. Lower ACC GABA/Cr levels were significantly associated with greater impulsivity and worse response inhibition, with relationships being most pronounced for ACC GABA/Cr and No-Go response inhibition in adolescent males. CONCLUSIONS These data provide the first human developmental in vivo evidence confirming frontal lobe GABA maturation, which was linked to impulsiveness and cognitive control. These findings suggest that reduced GABA may be an important neurobiological mechanism in the immature adolescent brain, contributing to the reduced yet rapidly developing ability to inhibit risky behaviors and to make suboptimal decisions, which could compromise adolescent health and safety.

Animal Behavior Models: Increased Sensitivity to Stressors and Other Environmental Experiences after Prenatal Cocaine Exposurea

ABSTRACT: Neural compensations occurring after prenatal cocaine exposure may often permit some functional recovery, although the cost of this reorganization may be a decrease in adaptability. As we have seen in our rodent model of prenatal cocaine exposure, latent deficits may become unmasked when offspring are exposed to cognitive and environmental demands and stressors. In adolescence and adulthood, offspring exposed gestationally to cocaine exhibit characteristic decreases in stress‐induced immobility along with increases in aggression under the demands of social competition. Recently, we observed that cocaine‐exposed offspring are also unusually sensitive to the long‐term effects of early manipulation (noninvasive heart rate testing at 16 days of age). When tested in adulthood, cocaine‐exposed offspring not receiving this early experience exhibited less immobility when tested in the presence of intermittent footshock or when subsequently examined in an open field as well as more locomotion in the open field than control offspring, findings reminiscent of previous work. By contrast, these effects were normalized (shock‐induced immobility) or reversed (open field immobility and locomotion) in cocaine‐exposed animals given the early experience. This marked susceptibility to the effects of early manipulation was less evident in control offspring and even in a group of stunted nutritional controls. Thus, cocaine‐exposed offspring may exhibit increased sensitivity not only to environmental demands and stressors, but also to the potential moderating or beneficial effects of early experiences.

Methadone maintenance improves cognitive performance after two months of treatment.

Methadone maintenance (MM) has received little scientific attention regarding neurocognitive effects. The present study examined cognitive function in 17 opiate-dependent subjects at baseline and after 2 months of MM treatment. Subjects demonstrated significant improvements from baseline on measures of verbal learning and memory, visuospatial memory, and psychomotor speed and reduced frequency of drug use (Addiction Severity Index) relative to baseline, although the total percentage of urine samples positive for additional illicit substances was slightly increased. No effect of illicit drug use was observed when the sample was stratified by urine toxicology results, suggesting that improvements in cognition were not associated with additional illicit drug use. Results suggest that opiate-dependent subjects exhibit significant improvement in cognitive function after MM treatment. Future investigations are needed to confirm these findings.

Cocaine and development: A retrospective perspective

Neurobehavioral alterations evident in offspring of Sprague-Dawley rat dams exposed to 40 mg/kg/day cocaine subcutaneously from gestational days 8-20 are reviewed. Consequences for offspring are often age dependent: for instance, reliable deficits in classical conditioning are evident during the early postnatal period, whereas cognitive effects are less pervasive in adulthood, although apparent in tasks such as reversal training. Gender of offspring is another variable of importance, particularly when testing animals in adulthood, with adult male offspring being more likely than their female counterparts to exhibit alterations following the prenatal exposure regimen. Characteristics of the test situation likewise influence detection of outcome effects, with effects particularly likely to emerge under stressful testing conditions or other challenges to the organism. Under these circumstances, alterations in responsiveness to stressors also sometimes emerged in offspring of pair-fed (PF) dams (whose food intake was restricted to match that of cocaine-exposed [COC] dams); these findings perhaps should not be surprising given that pair feeding is a stressor and prenatal stress is known to alter later stressor responsiveness. Although several approaches to equate food intake or avoid pair feeding have yielded disappointing findings, one promising approach is to initiate cocaine administration prior to mating followed by exposure throughout gestation. Premating exposure to cocaine was sufficient to eliminate anorexic effects of drug delivery during pregnancy, although it remains to be seen how similar the pattern of neurobehavioral alterations that emerge with this extended exposure regimen will be to effects seen following more restricted gestational exposure.