Filbey, Francesca M.

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Francesca Filbey holds the Bert Moore Chair in BrainHealth and is the head of the Filbey Lab at the Center for BrainHealth. Dr. Filbey's research interests are focused on addictive disorders, specifically substance abuse and overeating. "The overarching goal across my line of translational research is to characterize factors that increase risk for addictive disorders. Specifically, I am interested in how early life factors such as period of exposure (e.g., adolescent onset of regular use) or early life stress mediate the neural mechanisms that are associated with addictive disorders, and how genetic risk moderates these effects." For more information about Professor Filbey see her Filbey Lab pages, her BBS People page and her Center for BrainHealth Researcher page.

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    Adolescents Show Differential Dysfunctions Related to Alcohol and Cannabis Use Disorder Severity in Emotion and Executive Attention Neuro-Circuitries
    (Elsevier Inc.) Aloi, J.; Blair, K. S.; Crum, K. I.; Meffert, H.; White, S. F.; Tyler, P. M.; Thornton, L. C.; Mobley, A. M.; Killanin, A. D.; Adams, K. O.; Filbey, Francesca M.; Pope, K.; Blair, R. J. R.; 0000 0001 3618 6298 (Filbey, FM); Filbey, Francesca M.
    Alcohol and cannabis are two substances that are commonly abused by adolescents in the United States and which, when abused, are associated with negative medical and psychiatric outcomes across the lifespan. These negative psychiatric outcomes may reflect the detrimental impact of substance abuse on neural systems mediating emotion processing and executive attention. However, work indicative of this has mostly been conducted either in animal models or adults with Alcohol and/or Cannabis Use Disorder (AUD/CUD). Little work has been conducted in adolescent patients. In this study, we used the Affective Stroop task to examine the relationship in 82 adolescents between AUD and/or CUD symptom severity and the functional integrity of neural systems mediating emotional processing and executive attention. We found that AUD symptom severity was positively related to amygdala responsiveness to emotional stimuli and negatively related to responsiveness within regions implicated in executive attention and response control (i.e., dorsolateral prefrontal cortex, anterior cingulate cortex, precuneus) as a function of task performance. In contrast, CUD symptom severity was unrelated to amygdala responsiveness but positively related to responsiveness within regions including precuneus, posterior cingulate cortex, and inferior parietal lobule as a function of task performance. These data suggest differential impacts of alcohol and cannabis abuse on the adolescent brain.
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    Preliminary Findings Demonstrating Latent Effects of Early Adolescent Marijuana Use Onset on Cortical Architecture
    (Elsevier Sci Ltd) Filbey, Francesca M.; McQueeny, Tim; DeWitt, Samuel J.; Mishra, Virendra; 0000 0001 3618 6298 (Filbey, FM); Filbey, Francesca M.; McQueeny, Tim; DeWitt, Samuel J.
    Background: As the most commonly used illicit substance during early adolescence, long-term or latent effects of early adolescent marijuana use across adolescent developmental processes remain to be determined. Methods: We examined cortical thickness, gray/white matter border contrast (GWR) and local gyrification index (LGI) in 42 marijuana (MJ) users. Voxelwise regressions assessed early-onset (age = 16 years-old) differences and relationships to continued use while controlling for current age and alcohol use. Results: Although groups did not differ by onset status, groups diverged in their correlations between cannabis use and cortical architecture. Among early-onset users, continued years of MJ use and current MJ consumption were associated with thicker cortex, increased GWR and decreased LGI. Late-onset users exhibited the opposite pattern. This divergence was observed in all three morphological measures in the anterior dorsolateral frontal cortex (p < .05, FWE-corrected). Conclusions: Divergent patterns between current MJ use and elements of cortical architecture were associated with early MJ use onset. Considering brain development in early adolescence, findings are consistent with disruptions in pruning. However, divergence with continued use for many years thereafter suggests altered trajectories of brain maturation during late adolescence and beyond.
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    Long-Term Effects of Marijuana Use on the Brain
    (Natl Acad Sciences) Filbey, Francesca M.; Aslan, Sina; Calhoun, Vince D.; Spence, Jeffrey S.; Damaraju, Eswar; Caprihan, Arvind; Segall, Judith; 0000 0001 3618 6298 (Filbey, FM); J-5163-2014 (Filbey, FM); Filbey, Francesca M.; Aslan, Sina; Spence, Jeffrey S.
    Questions surrounding the effects of chronic marijuana use on brain structure continue to increase. To date, however, findings remain inconclusive. In this comprehensive study that aimed to characterize brain alterations associated with chronic marijuana use, we measured gray matter (GM) volume via structural MRI across the whole brain by using voxel-based morphology, synchrony among abnormal GM regions during resting state via functional connectivity MRI, and white matter integrity (i.e., structural connectivity) between the abnormal GM regions via diffusion tensor imaging in 48 marijuana users and 62 age- and sex-matched nonusing controls. The results showed that compared with controls, marijuana users had significantly less bilateral orbitofrontal gyri volume, higher functional connectivity in the orbitofrontal cortex (OFC) network, and higher structural connectivity in tracts that innervate the OFC (forceps minor) as measured by fractional anisotropy (FA). Increased OFC functional connectivity in marijuana users was associated with earlier age of onset. Lastly, a quadratic trend was observed suggesting that the FA of the forceps minor tract initially increased following regular marijuana use but decreased with protracted regular use. This pattern may indicate differential effects of initial and chronic marijuana use that may reflect complex neuroadaptive processes in response to marijuana use. Despite the observed age of onset effects, longitudinal studies are needed to determine causality of these effects.
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    Automatic and Reproducible Positioning of Phase-Contrast MRI for the Quantification of Global Cerebral Blood Flow
    (Public Library of Science) Liu, Peiying; Lu, Hanzhang; Filbey, Francesca M.; Pinkham, Amy E.; McAdams, Carrie J.; Adinoff, Bryon; Daliparthi, Vamsi; Cao, Yan; 0000 0001 3618 6298 (Filbey, FM); 0000 0001 2904 8428 (Cao, Y); 11522796 (Cao, Y); Filbey, Francesca M.; Cao, Yan
    Phase-Contrast MRI (PC-MRI) is a noninvasive technique to measure blood flow. In particular, global but highly quantitative cerebral blood flow (CBF) measurement using PC-MRI complements several other CBF mapping methods such as arterial spin labeling and dynamic susceptibility contrast MRI by providing a calibration factor. The ability to estimate blood supply in physiological units also lays a foundation for assessment of brain metabolic rate. However, a major obstacle before wider applications of this method is that the slice positioning of the scan, ideally placed perpendicular to the feeding arteries, requires considerable expertise and can present a burden to the operator. In the present work, we proposed that the majority of PC-MRI scans can be positioned using an automatic algorithm, leaving only a small fraction of arteries requiring manual positioning. We implemented and evaluated an algorithm for this purpose based on feature extraction of a survey angiogram, which is of minimal operator dependence. In a comparative test-retest study with 7 subjects, the blood flow measurement using this algorithm showed an inter-session coefficient of variation (CoV) of 4.07 ± 3.03%. The Bland-Altman method showed that the automatic method differs from the manual method by between -8% and 11%, for 95% of the CBF measurements. This is comparable to the variance in CBF measurement using manually-positioned PC MRI alone. In a further application of this algorithm to 157 consecutive subjects from typical clinical cohorts, the algorithm provided successful positioning in 89.7% of the arteries. In 79.6% of the subjects, all four arteries could be planned using the algorithm. Chi-square tests of independence showed that the success rate was not dependent on the age or gender, but the patients showed a trend of lower success rate (p = 0.14) compared to healthy controls. In conclusion, this automatic positioning algorithm could improve the application of PC-MRI in CBF quantification.
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    Neural effects of positive and negative incentives during marijuana withdrawal
    Filbey, Francesca M.; Dunlop, Joseph; Myers, Ursula S.
    In spite of evidence suggesting two possible mechanisms related to drug-seeking behavior, namely reward-seeking and harm avoidance, much of the addiction literature has focused largely on positive incentivization mechanisms associated with addiction. In this study, we examined the contributing neural mechanisms of avoidance of an aversive state to drug-seeking behavior during marijuana withdrawal. To that end, marijuana users were scanned while performing the monetary incentive delay task in order to assess positive and negative incentive processes. The results showed a group x incentive interaction, such that marijuana users had greater response in areas that underlie reward processes during positive incentives while controls showed greater response in the same areas, but to negative incentives. Furthermore, a negative correlation between withdrawal symptoms and response in the amygdala during negative incentives was found in the marijuana users. These findings suggest that although marijuana users have greater reward sensitivity and less harm avoidance than controls, that attenuated amygdala response, an area that underlies fear and avoidance, was present in marijuana users with greater marijuana withdrawal symptoms. This is concordant with models of drug addiction that involve multiple sources of reinforcement in substance use disorders, and suggests the importance of strategies that focus on respective mechanisms.

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