38 research outputs found
Cigarette smoking is associated with amplified age-related volume loss in subcortical brain regions
BACKGROUND:
Magnetic resonance imaging studies of cigarette smoking-related effects on human brain structure have primarily employed voxel-based morphometry, and the most consistently reported finding was smaller volumes or lower density in anterior frontal regions and the insula. Much less is known about the effects of smoking on subcortical regions. We compared smokers and non-smokers on regional subcortical volumes, and predicted that smokers demonstrate greater age-related volume loss across subcortical regions than non-smokers.
METHODS:
Non-smokers (n=43) and smokers (n=40), 22-70 years of age, completed a 4T MRI study. Bilateral total subcortical lobar white matter (WM) and subcortical nuclei volumes were quantitated via FreeSurfer. In smokers, associations between smoking severity measures and subcortical volumes were examined.
RESULTS:
Smokers demonstrated greater age-related volume loss than non-smokers in the bilateral subcortical lobar WM, thalamus, and cerebellar cortex, as well as in the corpus callosum and subdivisions. In smokers, higher pack-years were associated with smaller volumes of the bilateral amygdala, nucleus accumbens, total corpus callosum and subcortical WM.
CONCLUSIONS:
Results provide novel evidence that chronic smoking in adults is associated with accelerated age-related volume loss in subcortical WM and GM nuclei. Greater cigarette quantity/exposure was related to smaller volumes in regions that also showed greater age-related volume loss in smokers. Findings suggest smoking adversely affected the structural integrity of subcortical brain regions with increasing age and exposure. The greater age-related volume loss in smokers may have implications for cortical-subcortical structural and/or functional connectivity, and response to available smoking cessation interventions
Aberrations of anterior insular cortex functional connectivity in nontreatment-seeking alcoholics
An emergent literature suggests that resting state functional magnetic resonance imaging (rsfMRI) functional connectivity (FC) patterns are aberrant in alcohol use disorder (AUD) populations. The salience network (SAL) is an established set of brain regions prominent in salience attribution and valuation, and includes the anterior insular cortex (AIC). The SAL is thought to play a role in AUD through directing increased attention to interoceptive cues of intoxication. There is very little information on the salience network (SAL) in AUD, and, in particular, there are no data on SAL FC in currently drinking, nontreatment seeking individuals with AUD (NTS). rsfMRI data from 16 NTS and 21 social drinkers (SD) were compared using FC correlation maps from ten seed regions of interest in the bilateral AIC. As anticipated, SD subjects demonstrated greater insular FC with frontal and parietal regions. We also found that, compared to SD, NTS had higher insular FC with hippocampal and medial orbitofrontal regions. The apparent overactivity in brain networks involved in salience, learning, and behavioral control in NTS suggests possible mechanisms in the development and maintenance of AUD
Differences in White Matter Microstructure and Connectivity in NontreatmentâSeeking Individuals with Alcohol Use Disorder
Background
Diffusionâweighted imaging (DWI) has been widely used to investigate the integrity of white matter (WM; indexed by fractional anisotropy [FA]) in alcohol dependence and cigarette smoking. These disorders are highly comorbid, yet cigarette use has often not been adequately controlled in neuroimaging studies of alcoholâdependent populations. In addition, information on WM deficits in currently drinking, nontreatmentâseeking (NTS) individuals with alcohol dependence is limited. Therefore, the aim of this work was to investigate WM microstructural integrity in alcohol use disorder by comparing matched samples of cigarette smoking NTS and social drinkers (SD).
Methods
Thirtyâeight smoking NTS and 19 smoking SD subjects underwent DWI as well as structural magnetic resonance imaging. After an inâhouse preprocessing of the DWI data, FA images were analyzed with tractâbased spatial statistics (TBSS). FA obtained from the TBSS skeleton was tested for correlation with recent alcohol consumption.
Results
Smoking NTS had lower FA relative to smoking SD, predominantly in the left hemisphere (p < 0.05, familyâwise error rate corrected across FA skeleton). Across the full sample, FA and number of drinks per week were negatively related (Ï = â0.348, p = 0.008). Qualitative analyses of the structural connections through compromised WM as identified by TBSS showed differential connectivity of gray matter in NTS compared to SD subjects of left frontal, temporal, and parietal regions.
Conclusions
NTS subjects had lower WM FA than SD, indicating compromised WM integrity in the NTS population. The inverse relationship of entire WM skeleton FA with selfâreported alcohol consumption supports previous evidence of a continuum of detrimental effects of alcohol consumption on WM. These results provide additional evidence that alcohol dependence is associated with reduced WM integrity in currently drinking NTS alcoholâdependent individuals, after controlling for the key variable of cigarette smoking
Monetary discounting and ventral striatal dopamine receptor availability in nontreatment-seeking alcoholics and social drinkers
RATIONALE: Dopamine (DA) in the ventral striatum (VST) has long been implicated in addiction pathologies, yet its role in temporal decision-making is not well-understood.
OBJECTIVES: To determine if VST DA D2 receptor availability corresponds with greater impulsive choice in both nontreatment-seeking alcoholics (NTS) and social drinkers (SD).
METHODS: NTS subjects (nâ=â10) and SD (nâ=â13) received PET scans at baseline with the D2/D3 radioligand [(11)C]raclopride (RAC). Outside the scanner, subjects performed a delay discounting procedure with monetary rewards. RAC binding potential (BPND) was estimated voxelwise, and correlations were performed to test for relationships between VST BPND and delay discounting performance. Self-reported impulsivity was also tested for correlations with BPND.
RESULTS: Across all subjects, greater impulsive choice for $20 correlated with lower BPND in the right VST. NTS showed greater impulsive choice than SD and were more impulsive by self-report. Across all subjects, the capacity of larger rewards to reduce impulsive choice (the magnitude effect) correlated negatively (pâ=â0.028) with problematic alcohol use (AUDIT) scores. Self-reported impulsivity did not correlate with BPND in VST.
CONCLUSIONS: Preference for immediate reinforcement may reflect greater endogenous striatal DA or lower D2 number, or both. Alcoholic status did not mediate significant effects on VST BPND, suggesting minimal effects from alcohol exposure. The apparent lack of BPND correlation with self-reported impulsivity highlights the need for objective behavioral assays in the study of the neurochemical substrates of behavior. Finally, our results suggest that the magnitude effect may be more sensitive to alcohol-induced problems than single discounting measures
Differential dopamine function in fibromyalgia
Approximately 30% of Americans suffer from chronic pain disorders, such as fibromyalgia (FM), which can cause debilitating pain. Many pain-killing drugs prescribed for chronic pain disorders are highly addictive, have limited clinical efficacy, and do not treat the cognitive symptoms reported by many patients. The neurobiological substrates of chronic pain are largely unknown, but evidence points to altered dopaminergic transmission in aberrant pain perception. We sought to characterize the dopamine (DA) system in individuals with FM. Positron emission tomography (PET) with [18F]fallypride (FAL) was used to assess changes in DA during a working memory challenge relative to a baseline task, and to test for associations between baseline D2/D3 availability and experimental pain measures. Twelve female subjects with FM and eleven female controls completed study procedures. Subjects received one FAL PET scan while performing a â2-backâ task, and one while performing a â0-backâ (attentional control, âbaselineâ) task. FM subjects had lower baseline FAL binding potential (BP) in several cortical regions relative to controls, including anterior cingulate cortex. In FM subjects, self-reported spontaneous pain negatively correlated with FAL BP in the left orbitofrontal cortex and parahippocampal gyrus. Baseline BP was significantly negatively correlated with experimental pain sensitivity and tolerance in both FM and CON subjects, although spatial patterns of these associations differed between groups. The data suggest that abnormal DA function may be associated with differential processing of pain perception in FM. Further studies are needed to explore the functional significance of DA in nociception and cognitive processing in chronic pain
Corticostriatal and dopaminergic response to beer flavor with both fMRI and [11C]raclopride Positron Emission Tomography
Background
Cue-evoked drug seeking behavior likely depends on interactions between frontal activity and ventral striatal (VST) dopamine transmission. Using [11C]raclopride (RAC) positron emission tomography (PET), we previously demonstrated that beer flavor (absent intoxication) elicited VST dopamine (DA) release in beer drinkers, inferred by RAC displacement. Here, a subset of subjects from this previous RAC-PET study underwent a similar paradigm during functional magnetic resonance imaging (fMRI) to test how orbitofrontal cortex (OFC) and VST BOLD responses to beer flavor are related to VST DA release and motivation to drink.
Methods
Male beer drinkers (n=28, age=24±2, drinks/week=16±10) from our previous PET study participated in a similar fMRI paradigm wherein subjects tasted their most frequently consumed brand of beer and GatoradeŸ (appetitive control). We tested for correlations between blood oxygenation level dependent (BOLD) activation in fMRI and VST DA responses in PET, and drinking-related variables.
Results
Compared to Gatorade, beer flavor increased wanting and desire to drink, and induced BOLD responses in bilateral OFC and right VST. Wanting and desire to drink correlated with both right VST and medial OFC BOLD activation to beer flavor. Like the BOLD findings, beer flavor (relative to Gatorade) again induced right VST DA release in this fMRI subject subset, but there was no correlation between DA release and the magnitude of BOLD responses in frontal regions of interest.
Conclusions
Both imaging modalities showed a right lateralized VST response (BOLD and DA release) to a drug-paired conditioned stimulus, whereas fMRI BOLD responses in the VST and medial OFC also reflected wanting and desire to drink. The data suggest the possibility that responses to drug-paired cues may be rightward biased in the VST (at least in right-handed males), and that VST and OFC responses in this gustatory paradigm reflect stimulus wanting
The Brain: Is it a Next Frontier to Better Understand the Regulation and Control of Hematopoiesis for Future Modulation and Treatment?
We wish to suggest the possibility there is a link between the brain and hematopoiesis in the bone marrow and that in the future it may be possible to use such information for better understanding of the regulation of hematopoiesis, and for efficacious treatment of hematopoietic disorders
Reliability of Striatal [11C]Raclopride Binding in Smokers Wearing Transdermal Nicotine Patches
PURPOSE:
In studies where [(11)C]raclopride (RAC) positron emission tomography (PET) is used to assess changes in striatal dopamine, it is important to control for cognitive states, such as drug craving, that could alter dopamine levels. In cigarette smokers, transdermal nicotine patches (TNP) can control nicotine craving, but the effects of nicotine patches on RAC binding are unknown. Thus, we sought to determine the test-retest reliability of RAC binding in the presence of nicotine patches.
METHODS:
Eleven male smokers were scanned twice with RAC on separate days while wearing TNP.
RESULTS:
Across the striatum, test-retest variability was 7.63 ± 5.88; percent change in binding potential was 1.11 ± 9.83; and the intraclass correlation coefficient was 0.91 (p < 0.0001).
CONCLUSION:
Baseline RAC binding is highly reproducible in smokers wearing nicotine patches. This suggests that TNP are an acceptable method for controlling cigarette craving during studies that utilize RAC to examine changes in dopamine
Olfactory identification in subjective cognitive decline and mild cognitive impairment: Association with tau but not amyloid positron emission tomography
Introduction
We investigated the association between olfactory identification and Alzheimer's disease biomarkers, including amyloid, tau, and neurodegeneration.
Methods
Thirty-four older adults, including 19 cognitively normal (CN), 10 subjective cognitive decline (SCD), and 5 mild cognitive impairment, underwent amyloid positron emission tomography, magnetic resonance imaging, and the University of Pennsylvania Smell Identification Test (UPSIT). Twenty-six also underwent tau positron emission tomography. Associations between the UPSIT and regionally sampled amyloid, tau, and temporal atrophy were evaluated. Voxel-wise regression models were also utilized. Analyses were conducted with the full sample and only CN/SCD.
Results
Lower UPSIT scores were associated with increased temporal and parietal tau burden in regional and voxel-wise analyses in the full sample and in CN and SCD only. Temporal lobe atrophy was associated with lower UPSIT score. Amyloid was not associated with the UPSIT.
Discussion
Impairment on the UPSIT may be a good marker for tau and neurodegeneration in preclinical or prodromal Alzheimer's disease