Delay discounting and alcohol consumption correlate with dorsal anterior insula activation during choice in nontreatment-seeking heavy drinkers.

BACKGROUND: The anterior insular cortex (AIC), a prominent salience network node, integrates interoceptive information and emotional states into decision making. While AIC activation during delay discounting (DD) in alcohol use disorder (AUD) has been previously reported, the associations between AIC activation, impulsive choice, alcohol consumption, and connectivity remain unknown. We therefore tested AIC brain responses during DD in heavy drinkers and their association with DD performance, alcohol drinking, and task-based connectivity. METHODS: Twenty-nine heavy drinkers (12 females; mean (SD) age=31.5 ± 6.1 years; mean (SD)=40.8 ± 23.4 drinks/week) completed a DD task during functional MRI. Regions activated during DD decision making were tested for correlation with DD behavior and alcohol drinking. Psychophysiological interaction (PPI) models assessed the task-dependent functional connectivity (FC) of activation during choice. RESULTS: Delay discounting choice activated bilateral anterior insular cortex, anterior cingulate cortex, and left precentral gyrus. Right dorsal (d) AIC activation during choice negatively correlated withdiscounting of delayed rewards and alcohol consumption. PPI analysis revealed FC of the right dAIC to both the anterior and posterior cingulate cortices-key nodes in the midline default mode network. CONCLUSIONS: Greater dAIC involvement in intertemporal choice may confer more adaptive behavior (lower impulsivity and alcohol consumption). Moreover, salience network processes governing discounting may require midline default mode (precuneus/posterior cingulate cortex) recruitment. These findings supporta key adaptive role for right dAIC in decision making involving future rewards and risky drinking.

Cerebral Blood Flow in the Salience Network of Individuals with Alcohol Use Disorder.

AIMS: Magnetic resonance imaging (MRI) studies have identified structural and functional differences in salience network nodes of individuals with alcohol use disorders (AUDs) after chronic exposure to alcohol. However, no studies have investigated cerebral blood flow (CBF) in nontreatment-seeking (NTS) individuals with AUD. METHODS: In this work, we sought to quantify putative CBF deficits in NTS individuals relative to social drinking (SD) controls and determine if CBF in the salience network is associated with AUD severity. Fifteen NTS (36.5 ± 11.2 years old, 30.0 ± 22.7 drinks/week) and 22 SD (35.6 ± 11.9 years old, 9.1 ± 5.7 drinks/week) underwent pseudocontinuous arterial spin labeling MRI. RESULTS: Compared with social drinkers, NTS individuals had significantly lower CBF in the right and left dorsal anterior insula, and the left ventral anterior and posterior insula. The Alcohol Use Disorder Identification Test (AUDIT) score showed a significant negative relationship with CBF in the bilateral caudal anterior cingulate cortex. In addition, a significant negative correlation was present between number of standard drinks consumed per week and the left frontal opercular CBF. CONCLUSION: These results provide evidence that insular CBF is negatively associated with heavy drinking, and that severity of alcohol use is related to CBF deficits in key nodes of the salience network. Longitudinal data are needed to understand if disruptions of CBF in the insula and the salience network are a predisposition for or a consequence of chronic AUD.

Resting state functional MRI in infants with prenatal opioid exposure-a pilot study.

PURPOSE: Exposure to prenatal opioids may adversely impact the developing brain networks. The aim of this pilot study was to evaluate alterations in amygdalar functional connectivity in human infants with prenatal opioid exposure. METHODS: In this prospective IRB approved study, we performed resting state functional MRI (rs-fMRI) in 10 infants with prenatal opioid exposure and 12 infants without prenatal drug exposure at < 48 weeks corrected gestational age. Following standard preprocessing, we performed seed-based functional connectivity analysis with the right and left amygdala as the regions of interest after correcting for maternal depression and infant sex. We compared functional connectivity of the amygdala network between infants with and without prenatal opioid exposure. RESULTS: There were significant differences in connectivity of the amygdala seed regions to the several cortical regions including the medial prefrontal cortex in infants who had prenatal opioid exposure when compared with opioid naïve infants. CONCLUSION: This finding of increased amygdala functional connectivity in infants with in utero opioid exposure suggests a potential role of maternal opioid exposure on infants' altered amygdala function. This association with prenatal exposure needs to be replicated in future larger studies.

Alterations in White Matter Microstructure and Connectivity in Young Adults with Alcohol Use Disorder.

BACKGROUND: Magnetic resonance imaging (MRI) studies have shown differences in volume and structure in the brains of individuals with alcohol use disorder (AUD). Most research has focused on neuropathological effects of alcohol that appear after years of chronic alcohol misuse. However, few studies have investigated white matter (WM) microstructure and diffusion MRI-based (DWI) connectivity during early stages of AUD. Therefore, the goal of this work was to investigate WM integrity and structural connectivity in emerging adulthood AUD subjects using both conventional DWI metrics and a novel connectomics approach. METHODS: Twenty-two AUD and 18 controls (CON) underwent anatomic and diffusion MRI. Outcome measures were scalar diffusion metrics and structural network connectomes. Tract-Based Spatial Statistics was used to investigate group differences in diffusion measures. Structural connectomes were used as input into a community structure procedure to obtain a coclassification index matrix (an indicator of community association strength) for each subject. Differences in coclassification and structural connectivity (indexed by streamline density) were assessed via the Network Based Statistics Toolbox. RESULTS: AUD had higher fractional anisotropy (FA) values throughout the major WM tracts, but also had lower FA values in WM tracts in the cerebellum and right insula (pTFCE  < 0.05). Mean diffusivity was generally lower in the AUD group (pTFCE  < 0.05). AUD had lower coclassification of nodes between ventral attention and default mode networks and higher coclassification between nodes of visual, default mode, and somatomotor networks. Additionally, AUD had higher fiber density between an adjacent pair of nodes within the default mode network. CONCLUSIONS: Our results indicate that emerging adulthood AUD subjects may have differential patterns of FA and distinct differences in structural connectomes compared with CON. These data suggest that such alterations in microstructure and structural connectivity may uniquely characterize early stages of AUD and/or a predisposition for development of AUD.

Differences in White Matter Microstructure and Connectivity in Nontreatment-Seeking Individuals with Alcohol Use Disorder.

BACKGROUND: Diffusion-weighted 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 alcohol-dependent populations. In addition, information on WM deficits in currently drinking, nontreatment-seeking (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: Thirty-eight smoking NTS and 19 smoking SD subjects underwent DWI as well as structural magnetic resonance imaging. After an in-house preprocessing of the DWI data, FA images were analyzed with tract-based 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, family-wise error rate corrected across FA skeleton). Across the full sample, FA and number of drinks per week were negatively related (ρ = -0.348, 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 self-reported 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 alcohol-dependent individuals, after controlling for the key variable of cigarette smoking.

Corticostriatal and Dopaminergic Response to Beer Flavor with Both fMRI and [(11) C]raclopride Positron Emission Tomography.

BACKGROUND: Cue-evoked drug-seeking behavior likely depends on interactions between frontal activity and ventral striatal (VST) dopamine (DA) transmission. Using [(11) C]raclopride (RAC) positron emission tomography (PET), we previously demonstrated that beer flavor (absent intoxication) elicited VST 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 blood oxygenation level-dependent (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/wk = 16 ± 10) from our previous PET study participated in a similar fMRI paradigm wherein subjects tasted their most frequently consumed brand of beer and Gatorade(®) (appetitive control). We tested for correlations between 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.

GWAS of longitudinal amyloid accumulation on 18F-florbetapir PET in Alzheimer's disease implicates microglial activation gene IL1RAP.

Brain amyloid deposition is thought to be a seminal event in Alzheimer's disease. To identify genes influencing Alzheimer's disease pathogenesis, we performed a genome-wide association study of longitudinal change in brain amyloid burden measured by (18)F-florbetapir PET. A novel association with higher rates of amyloid accumulation independent from APOE (apolipoprotein E) ε4 status was identified in IL1RAP (interleukin-1 receptor accessory protein; rs12053868-G; P = 1.38 × 10(-9)) and was validated by deep sequencing. IL1RAP rs12053868-G carriers were more likely to progress from mild cognitive impairment to Alzheimer's disease and exhibited greater longitudinal temporal cortex atrophy on MRI. In independent cohorts rs12053868-G was associated with accelerated cognitive decline and lower cortical (11)C-PBR28 PET signal, a marker of microglial activation. These results suggest a crucial role of activated microglia in limiting amyloid accumulation and nominate the IL-1/IL1RAP pathway as a potential target for modulating this process.

Cortical dopamine release during a behavioral response inhibition task.

Dopamine (DA) dysregulation within fronto-striatal circuitry may underlie impulsivity in alcohol and other substance use disorders. To date, no one has directly demonstrated DA release during a task requiring the control of impulsive behavior. The current study was conducted to determine whether a response inhibition task (stop signal task; SST) would elicit detectable extrastriatal DA release in healthy controls. We hypothesized that DA release would be detected in regions previously implicated in different aspects of inhibitory control. [(18) F]Fallypride (FAL) PET imaging was performed in nine healthy males (24.6 ± 4.1 y.o.) to assess changes in cortical DA during a SST relative to a baseline "Go" task. On separate days, subjects received one FAL scan during the SST, and one FAL scan during a "Go" control; task-order was counter-balanced across subjects. Parametric BPND images were generated and analyzed with SPM8. Voxel-wise analysis indicated significant SST-induced DA release in several cortical regions involved in inhibitory control, including the insula, cingulate cortex, orbitofrontal cortex, precuneus, and supplementary motor area. There was a significant positive correlation between stop signal reaction time and DA release in the left orbitofrontal cortex, right middle frontal gyrus, and right precentral gyrus. These data support the feasibility of using FAL PET to study DA release during response inhibition, enabling investigation of relationships between DA function and impulsive behavior.

Association of plasma and cortical amyloid beta is modulated by APOE ε4 status.

BACKGROUND: Apolipoprotein E (APOE) ε4 allele's role as a modulator of the relationship between soluble plasma amyloid beta (Aß) and fibrillar brain Aß measured by Pittsburgh compound B positron emission tomography ([(11)C]PiB PET) has not been assessed. METHODS: Ninety-six Alzheimer's Disease Neuroimaging Initiative participants with [(11)C]PiB scans and plasma Aß1-40 and Aß1-42 measurements at the time of PET scanning were included. Regional and voxelwise analyses of [(11)C]PiB data were used to determine the influence of APOE ε4 allele on association of plasma Aß1-40, Aß1-42, and Aß1-40/Aß1-42 with [(11)C]PiB uptake. RESULTS: In APOE ε4- but not ε4+ participants, positive relationships between plasma Aß1-40/Aß1-42 and [(11)C]PiB uptake were observed. Modeling the interaction of APOE and plasma Aß1-40/Aß1-42 improved the explained variance in [(11)C]PiB binding compared with using APOE and plasma Aß1-40/Aß1-42 as separate terms. CONCLUSIONS: The results suggest that plasma Aß is a potential Alzheimer's disease biomarker and highlight the importance of genetic variation in interpretation of plasma Aß levels.

Greater ventral striatal functional connectivity in cigarette smokers relative to non-smokers across a spectrum of alcohol consumption.

Cigarette smoking is associated with elevated risk of disease and mortality and contributes to heavy healthcare-related economic burdens. The nucleus accumbens is implicated in numerous reward-related behaviors, including reinforcement learning and incentive salience. The established functional connectivity of the accumbens includes regions associated with motivation, valuation, and affective processing. Although the high comorbidity of cigarette smoking with drinking behaviors may collectively affect brain activity, there could be independent effects of smoking in alcohol use disorder that impact brain function and behavior. We hypothesized that smoking status, independent of alcohol use, would be associated with aberrations of nucleus accumbens functional connectivity to brain regions that facilitate reward processing, salience attribution, and inhibitory control. Resting state functional magnetic resonance imaging data from thirty-one nonsmokers and nineteen smoking individuals were analyzed using seed-based correlations of the bilateral accumbens with all other brain voxels. Statistical models accounted for drinks consumed per week. The smoking group demonstrated significantly higher functional connectivity between the left accumbens and the bilateral insula and anterior cingulate cortex, as well as hyperconnectivity between the right accumbens and the insula. Confirmatory analyses using the insula and cingulate clusters generated from the original analysis as seed regions reproduced the hyperconnectivity in smokers between the bilateral insular regions and the accumbens. In conclusion, smoking status had distinct effects on neural activity; hyperconnectivity between the accumbens and insula in smokers may reflect enhanced encoding of the reinforcing effects of smoking and greater orientation toward smoking-associated stimuli.

Effects of acute alcohol exposure and chronic alcohol use on neurite orientation dispersion and density imaging (NODDI) parameters.

RATIONALE: Little is known about how acute and chronic alcohol exposure may alter the in vivo membrane properties of neurons. OBJECTIVES: We employed neurite orientation dispersion and density imaging (NODDI) to examine acute and chronic effects of alcohol exposure on neurite density. METHODS: Twenty-one healthy social drinkers (CON) and thirteen nontreatment-seeking individuals with alcohol use disorder (AUD) underwent a baseline multi-shell diffusion magnetic resonance imaging (dMRI) scan. A subset (10 CON, 5 AUD) received dMRI during intravenous infusions of saline and alcohol during dMRI. NODDI parametric images included orientation dispersion (OD), isotropic volume fraction (ISOVF), and corrected intracellular volume fraction (cICVF). Diffusion tensor imaging metrics of fractional anisotropy and mean, axial, and radial diffusivity (FA, MD, AD, RD) were also computed. Average parameter values were extracted from white matter (WM) tracts defined by the Johns Hopkins University atlas. RESULTS: There were group differences in FA, RD, MD, OD, and cICVF, primarily in the corpus callosum. Both saline and alcohol had effects on AD and cICVF in WM tracts proximal to the striatum, cingulate, and thalamus. This is the first work to indicate that acute fluid infusions may alter WM properties, which are conventionally believed to be insensitive to acute pharmacological challenges. It also suggests that the NODDI approach may be sensitive to transient changes in WM. The next steps should include determining if the effect on neurite density differs with solute or osmolality, or both, and translational studies to assess how alcohol and osmolality affect the efficiency of neurotransmission.

Amyloid and tau pathology are associated with cerebral blood flow in a mixed sample of nondemented older adults with and without vascular risk factors for Alzheimer's disease.

Identification of biomarkers for the early stages of Alzheimer's disease (AD) is an imperative step in developing effective treatments. Cerebral blood flow (CBF) is a potential early biomarker for AD; generally, older adults with AD have decreased CBF compared to normally aging peers. CBF deviates as the disease process and symptoms progress. However, further characterization of the relationships between CBF and AD risk factors and pathologies is still needed. We assessed the relationships between CBF quantified by arterial spin-labeled magnetic resonance imaging, hypertension, APOEε4, and tau and amyloid positron emission tomography in 77 older adults: cognitively normal, subjective cognitive decline, and mild cognitive impairment. Tau and amyloid aggregation were related to altered CBF, and some of these relationships were dependent on hypertension or APOEε4 status. Our findings suggest a complex relationship between risk factors, AD pathologies, and CBF that warrants future studies of CBF as a potential early biomarker for AD.

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.

Imaging of alcohol-induced dopamine release in rats:preliminary findings with [(11) C]raclopride PET.

Microdialysis studies report that systemic alcohol increases extracellular dopamine (DA) in the rat striatum. The present study examined whether changes in striatal DA could be detected in rats using small animal positron emission tomography (PET). PET images were acquired in 44 alcohol-naïve male Wistar and alcohol-preferring (P) rats. Subjects received up to three [(11) C]raclopride scans (rest, alcohol, and saline). Animals were anesthetized with isoflurane and secured on a stereotactic-like holder during all scans. Blood samples were collected from the tail or lateral saphenous vein of 12 animals 10 min after tracer injection for determination of blood alcohol concentration (BAC). Time activity curves were extracted from the striatum and the cerebellum and binding potential (BP(ND) ) was calculated as a measure of D(2) receptor availability. Wistars given 1.0 g kg(-1) alcohol (20%v/v) i.v. or 3.0 g kg(-1) alcohol (20%v/v) i.p. showed significant alcohol-induced decreases in BP(ND) . In P rats (given 1.5, 2.25, or 3.0 g kg(-1) alcohol), no individual group showed a statistical effect of alcohol on BP(ND) , but taken together, all P rats receiving i.p. alcohol had significantly lower BP(ND) than rest or saline scans. Large decreases in BP(ND) were primarily observed in rats with BAC above 200 mg%. Also, a significant difference was found between baseline BP(ND) of Wistars who had undergone jugular catheterization surgery for i.v. alcohol administration and those who had not. Preliminary results suggest that alcohol-induced DA release in the rat striatum is detectable using small animal PET given sufficiently large cohorts and adequate blood alcohol levels.

Test-retest variability of [¹¹C]raclopride-binding potential in nontreatment-seeking alcoholics.

Knowledge of the reproducibility of striatal [¹¹C]raclopride (RAC) binding is important for studies that use RAC PET paradigms to estimate changes in striatal dopamine (DA) during pharmacological and cognitive challenges. To our knowledge, no baseline test-retest data exist for nontreatment-seeking alcoholics (NTS). We determined the test-retest reproducibility of baseline RAC binding potential (BP(ND) ) in 12 male NTS subjects. Subjects were scanned twice with single-bolus RAC PET on separate days. Striatal RAC BP (BP(ND) ) for left and right dorsal caudate, dorsal putamen, and ventral striatum was estimated using the Multilinear Reference Tissue Method (MRTM) and Logan Graphical Analysis (LGA) with a reference region. Test-retest variability (TRV), % change in BP(ND) between scan days, and the intraclass correlation coefficient (ICC) were used as metrics of reproducibility. For MRTM, TRV for striatal RAC binding in NTS subjects was ±6.5% and ±7.1% for LGA. Average striatal ICCs were 0.94 for both methods (P < 0.0001). Striatal BP(ND) values were similar to those reported previously for detoxified alcoholics. The results demonstrate that baseline striatal RAC binding is highly reproducible in NTS subjects, with a low variance similar to that reported for healthy control subjects.

Striatal dopamine transporter availability in unmedicated bipolar disorder.

OBJECTIVES: Dopamine transmission abnormalities have been implicated in the etiology of bipolar disorder (BPD). However, there is a paucity of receptor imaging studies in BPD, and little information is available about the dopamine system in BPD. Reuptake of synaptic dopamine by the dopamine transporter (DAT) is the principal mechanism regulating dopamine neurotransmission, and is often used as a marker for presynaptic dopamine function. This positron emission tomography (PET) study investigated whether DAT availability differed between BPD and healthy control subjects. METHODS: A total of 11 unmedicated BPD patients in either the euthymic or depressed phase and 13 closely matched healthy subjects underwent PET imaging with the DAT-selective radiotracer [(11) C]CFT and a structural magnetic resonance imaging (MRI) scan. Striatal binding potential (BP(ND) ) was estimated using the multilinear reference tissue model. Region of interest and analyses were conducted to test for differences in [(11) C]CFT BP(ND) between groups. RESULTS: Unmedicated BPD subjects had significantly lower DAT availability relative to healthy controls in bilateral dorsal caudate. CONCLUSIONS: The results of this study support the hypothesis that there are abnormalities in the dopaminergic system in BPD, and suggest that DAT availability may be related to the neuropathology of BPD. Future studies are needed to determine if DAT availability cycles with disease phase.

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.

Anterior cingulate cortex metabolites and white matter microstructure: a multimodal study of emergent alcohol use disorder.

Multimodal imaging is increasingly used to address neuropathology associated with alcohol use disorder (AUD). Few studies have investigated relationships between metabolite concentrations and white matter (WM) integrity; currently, there are no such data in AUD. In this preliminary study, we used complementary neuroimaging techniques, magnetic resonance spectroscopy (MRS), and diffusion weighted imaging (DWI), to study AUD neurophysiology. We tested for relationships between metabolites in the dorsal anterior cingulate cortex (dACC) and adjacent WM microstructure in young adult AUD and control (CON) subjects. Sixteen AUD and fourteen CON underwent whole-brain DWI and MRS of the dACC. Outcomes were dACC metabolites, and diffusion tensor metrics of dACC-adjacent WM. Multiple linear regression terms included WM region, group, and region × group for prediction of dACC metabolites. dACC myo-inositol was positively correlated with axial diffusivity in the left anterior corona radiata (p < 0.0001) in CON but not AUD (group effect: p < 0.001; region × group: p < 0.001; Bonferroni-corrected). In the bilateral anterior corona radiata and right genu of the corpus callosum, glutamate was negatively related to mean diffusivity in AUD, but not CON subjects (all model terms: p < 0.05, uncorrected). In AUD subjects, dACC glutamate was negatively correlated with AUD symptom severity. This is likely the first integrative study of cortical metabolites and WM integrity in young individuals with AUD. Differential relationships between dACC metabolites and adjacent WM tract integrity in AUD could represent early consequences of hazardous drinking, and/or novel biomarkers of early-stage AUD. Additional studies are required to replicate these findings, and to determine the behavioral relevance of these results.

Does Chronic Cannabis Use Impact Risky Decision-Making: An Examination of fMRI Activation and Effective Connectivity?

With the increase in use of cannabis and its shifting legal status in the United States, cannabis use has become an important research focus. While studies of other drug populations have shown marked increases in risky decision-making, the literature on cannabis users is not as clear. The current study examined the performance of 17 cannabis users and 14 non-users on the Balloon Analog Risk Task (BART) using behavioral, fMRI and effective connectivity methods. Significant attenuation was found in a functional pathway projecting from the dorsal anterior cingulate cortex (dACC) to the nucleus accumbens (NAc) in cannabis users compared to non-using controls as well as decreases in risk-taking behaviors. These findings suggest that cannabis users may process and evaluate risks and rewards differently than non-users.

A rat head holder for simultaneous scanning of two rats in small animal PET scanners: design, construction, feasibility testing and kinetic validation.

UNLABELLED: To reduce imaging costs, we designed a head holder for scanning two rats simultaneously in small animal PET scanners. Our goals were (i) to maintain high sensitivity and (ii) to minimize repositioning error between scans. METHODS: A semi-stereotaxic dual rat head holder was designed and constructed for dual rat scanning in our IndyPET-II scanner and the commercial microPET P4. It was also used for single rat scanning in a small-bore, high-resolution animal scanner ("ISAP"). Positional repeatability was validated via multiple [11C]Raclopride scans of a single rat on different days. Accuracy of repositioning was determined by visual comparison of images, and by metrics derived through image alignment. Kinetic validation was assessed via analysis of [18F]Fluorodeoxyglucose ([18F]FDG) dynamic PET studies of six rats. Each rat was scanned twice: once individually, with brain positioned at the center of field of view (CFOV), and once with a partner, with brain away from CFOV. Both rats were injected with FDG during each dual rat session. Patlak uptake constants (Ki) were calculated from whole brain images. Effects of attenuation and scatter correction on single versus dual scan images were explored. RESULTS: Image comparison and alignment metrics indicated excellent repositioning of rats. Scaled time-activity-curves from single and dual rat scans were indistinguishable. Average single and dual scan Ki values differed by only 6.3+/-7.5%. CONCLUSION: Dual rat scanning in a semi-stereotaxic holder is practical for economical small animal scanning and does not compromise kinetic accuracy of [18F]FDG dynamic scan data.