Faculty Bibliography

RATIONALE/BACKGROUND:Tobacco use for many people is compulsive in nature. Compelling theories of how smoking becomes compulsive exist but are largely based on extrapolation from neuroscience findings. Research on smokers is impeded, in part, by a lack of instruments that specifically measure compulsive smoking. OBJECTIVE:This study evaluated the measurement structure and validity of the Obsessive Compulsive Smoking Scale (OCSS), a ten-item questionnaire designed to measure compulsive smoking. METHODS:Participants were 239 daily smokers (>/=1 cigarette/day), including 142 students at a public university in Chicago and 97 veterans treated at the VA Boston Healthcare System. The OCSS and questionnaires measuring current and past smoking, cigarette craving, automatic smoking, and nicotine dependence were administered. RESULTS:Factor analysis with maximum likelihood extraction and oblique rotation revealed two correlated underlying factors, interpreted as "Preoccupation with Smoking" and "Compulsive Drive." The measurement structure was consistent across students and veterans, and confirmed in an independent sample of adults (n = 95). Veterans exhibited higher OCSS scores (full scale and subscales) than students. Across groups, higher OCSS scores were positively correlated with smoking intensity, craving, and nicotine dependence. OCSS full-scale and compulsive drive scores, but not smoking preoccupation scores, were inversely correlated with past month smoking reduction and minutes since last cigarette. CONCLUSIONS:The OCSS is a valid and reliable inventory for measuring the degree to which daily smokers are preoccupied with smoking and engage in compulsive tobacco use, and may be useful for advancing understanding of core smoking phenotypes or for tailoring cessation therapies.

Previous literature has reported effects of nicotine withdrawal on brain function during cognitive tasks such as verbal working memory (VWM). Mechanisms of these withdrawal effects have not been clearly identified. Functional neuroimaging offers an objective method to examine brain mechanisms associated with observable behavior and subjective reports. To investigate these mechanisms, 12 smokers were administered a 2-Back VWM challenge during two functional magnetic resonance imaging sessions. Participants abstained from smoking prior to both sessions; however, they applied a nicotine patch before one session and a placebo patch prior to the other. Among regions that exhibited a significant response to the 2-Back during either session, withdrawal was associated with significantly greater deactivation in left and right temporal poles and left medial frontal gyrus. The magnitude of task-related activation showed a significant inverse relationship to craving in the majority of regions during placebo administration. Also, individual brain responses varied more during placebo, suggesting inefficient neural processing. Results suggest that differences in brain response to a VWM challenge during abstinence may be attributed to increased craving. Further deactivation of regions associated with the default network (medial frontal and anterior temporal clusters) during the placebo condition suggests further suspension of default activity, possibly to compensate for inefficient neural processing.

BACKGROUND: Heterotaxy with polysplenia is associated with many cardiovascular anomalies including the occasional occurrence of congenital extrahepatic portosystemic shunts (CEPS). Missing this anomaly can lead to inappropriate and ineffective therapy. OBJECTIVE: To emphasize the importance and associated anatomy of CEPS in conjunction with heterotaxy with polysplenia. MATERIALS AND METHODS: Review of three young children who presented with cyanosis and pulmonary hypertension without a cardiac etiology. They were known (1) or discovered (2) to have heterotaxy with polysplenia. RESULTS: There was absence of the intrahepatic inferior vena cava (IVC) with azygos or hemiazygos continuation in all three cases. In spite of normal liver function, they were discovered to have large portosystemic shunts, splenorenal in location, along with diffuse peripheral pulmonary arterial dilatation suggestive of CEPS (Abernethy malformation) with hepatopulmonary or, more accurately, portopulmonary syndrome. All CEPS were ipsilateral to the spleens. Patency of the portal veins in these cases allowed for percutaneous shunt closure with resolution of cyanosis. CONCLUSION: CEPS is associated with heterotaxy with polysplenia and can be symptomatic because of pulmonary arteriovenous (AV) shunting. Portal and hepatic vein patency are critical for determining feasibility of CEPS closure.

BACKGROUND: We hypothesized that changes in vascular flow dynamics resulting from age and cardiovascular disease (CVD) would correlate to neurocognitive capacities, even in adults screened to exclude dementia and neurological disease. We studied endothelial-dependent as well as endothelial-independent brachial responses in older adults with CVD to study the associations of vascular responses with cognition. Comprehensive neurocognitive testing was used to discern which specific cognitive domain(s) correlated to the vascular responses. METHODS: Eighty-eight independent, community-dwelling older adults (70.02+7.67 years) with mild to severe CVD were recruited. Enrollees were thoroughly screened to exclude neurological disease and dementia. Flow-mediated (endothelial-dependent) and nitroglycerin-mediated (endothelial-independent) brachial artery responses were assessed using 2-d ultrasound. Cognitive functioning was assessed using comprehensive neuropsychological testing. Linear regression analyses were used to evaluate the relationships between the endothelial-dependent and endothelial-independent vascular flow dynamics and specific domains of neurocognitive function. RESULTS: Endothelial-dependent and endothelial-independent brachial artery responses both correlated with neurocognitive testing indices. The strongest independent relationship was between endothelial function and measures of attention-executive functioning. CONCLUSIONS: Endothelial-dependent and endothelial-independent vascular responsiveness correlate with neurocognitive performance among older CVD patients, particularly in the attention-executive domain. While further study is needed to substantiate causal relationships, our data demonstrate that brachial responses serve as important markers of risk for common neurocognitive changes. Learning and behavior-modifying therapeutic strategies that compensate for such common, insidious neurocognitive limitations will likely improve caregiving efficacy.

BACKGROUND:Previous studies have examined the impact of early life stress (ELS) on the gross morphometry of brain regions, including the corpus callosum. However, studies have not examined the relationship between ELS and the microstructural integrity of the brain. METHODS:In the present study we evaluated this relationship in healthy non-clinical participants using diffusion tensor imaging (DTI) and self-reported history of ELS. RESULTS:Regression analyses revealed significant reductions in fractional anisotropy (FA) within the genu of the corpus callosum among those exposed to the greatest number of early life stressors, suggesting reduced microstructural integrity associated with increased ELS. These effects were most pronounced in the genu of the corpus callosum compared to the body and splenium, and were evident for females rather than males despite no differences in total ELS exposure between the sexes. In addition, a further comparison of those participants who were exposed to no ELS vs. three or more ELS events revealed lower FA in the genu of the corpus callosum among the ELS-exposed group, with trends of FA reduction in the body and the whole corpus callosum. By contrast, there were no relationships between ELS and volumetric analysis of the CC regions. The two group did not differ significantly on measures of current depression, stress or anxiety. CONCLUSION/CONCLUSIONS:Our results reveal that greater exposure to ELS is associated with microstructural alterations in the white matter in the absence of significant volumetric changes. Importantly, our results indicate that exposure to ELS is associated with abnormalities on DTI despite the absence of clinically significant psychiatric symptoms. Future studies are needed to determine whether specific types of ELS are more likely to impact brain structure and function.

Results from recent studies suggest that chronic cigarette smoking is associated with increased white matter volume in the brain as determined by in vivo neuroimaging. We used diffusion tensor imaging to examine the microstructural integrity of the white matter in 10 chronic smokers and 10 nonsmokers. All individuals were healthy, without histories of medical or psychiatric illness. Fractional anisotropy (FA) and trace were measured in the genu, body, and splenium of the corpus callosum. FA provides a measure of directional versus nondirectional water diffusion, whereas trace provides a measure of nondirectional water diffusion. Lower FA and higher trace values are considered to reflect less brain integrity. Voxel-based morphometry was used to define volumes in each of these regions of the corpus callosum. Chronic smokers exhibited significantly higher FA in the body and whole corpus callosum and a strong trend for higher FA in the splenium compared with nonsmokers. FA did not differ between groups in the genu, and neither trace nor white matter volumes differed between groups in any of the regions of interest. When subdivided by Fagerström score (low vs. high), the low Fagerström group exhibited significantly higher FA in the body of the corpus callosum compared with the high Fagerström group and the nonsmokers. These results suggest that, among healthy adults, lower exposure to cigarette smoking is associated with increased microstructural integrity of the white matter compared with either no exposure or higher exposure. Additional studies are needed to further explore differences in white matter integrity between smokers and nonsmokers.

To achieve greater understanding of the brain mechanisms underlying nicotine craving in female smokers, we examined the influence of nicotine non-abstinence vs. acute nicotine abstinence on cue-elicited activation of the ventral striatum. Eight female smokers underwent an event-related functional magnetic resonance imaging (fMRI) paradigm presenting randomized sequences of smoking-related and non-smoking related pictures. Participants were asked to indicate by a key press the gender of individuals in smoking-related and non-smoking related pictures (gender discrimination task), to maintain and evaluate attention to the pictures. There was a significant effect of smoking condition on reaction times (RT) for a gender discrimination task intended to assess and maintain attention to the photographs-suggesting a deprivation effect of acute nicotine abstinence and a statistical trend indicating greater RTs for smoking cues than neutral cues. BOLD contrast (smoking vs. non-smoking cues) was greater in the non-abstinent vs. acutely abstinent conditions in the ventral striatum including the nucleus accumbens (VS/NAc). Moreover, a significant positive correlation was observed between baseline cigarette craving prior to scanning and VS/NAc activation (r=0.84, p=0.009), but only in the non-abstinent condition. These results may either be explained by ceiling effects of nicotine withdrawal in the abstinent condition or, may indicate reduced relative activation (smoking vs. neutral contrast) in the VS/NAc in the abstinent vs. non-abstinent conditions in this group of female smokers.