Grant Number:	1R35CA197461-01 Interpret this number
Primary Investigator:	Lerman, Caryn
Organization:	University Of Pennsylvania
Project Title:	Neuroscience-Based Interventions for Cancer Risk Behavior Change
Fiscal Year:	2015

¿ DESCRIPTION (provided by applicant): Tobacco use and obesity account for over 45% of preventable cancer deaths. Yet, these cancer risk behaviors are resistant to long-term change, despite widespread knowledge of the risks. Even with the best treatments available, most people revert to their former practices of cigarette smoking or eating. While behavior change interventions may address the habitual nature of these behaviors, they do not tackle the disruptive brain processes that undermine sustainable behavior change. Tobacco use and obesity are associated with cognitive impairments and altered brain functions that can interfere with the maintenance of goal-directed behaviors. More specifically, work in my laboratory points to the central role of alterations in working memory-related activation in the dorsolateral prefrontal cortices (DLPFC). DLPFC is at the core of the brain's cognitive control network, which supports planning, decision- making, and cognitive (self) control. Importantly, our pilot data show that DLPFC function can be safely restored using a novel and low-cost neuroscience-based intervention. Thus, the bold premise of this application is that it is possible to enhance th brain's capacity to over-ride behavioral habits that contribute to obesity and cigarette smoking, and ultimately to cancer. Broad Plan: Extending our pilot work, the proposed 7-year research plan begins with a Proof of Mechanism experiment to validate the effects of DLPFC-targeted transcranial direct current brain stimulation (tDCS) with cognitive training. Progressing to the Proof of Principle stage, experiments will identify the optimal type of cognitive training to complement tDCS and the optimal number of treatment sessions, with a focus on intermediate endpoints (e.g., cognitive function, risky decision-making, self-reported behaviors). In the final stage of the research plan, Phase II randomized controlled clinical trials will evaluate the efficacy of the optimized neuroscience-based interventions for individuals seeking treatment for smoking cessation (Study 1) and weight loss (Study 2). The deliverables are efficacious neuroscience-based interventions to be validated in Phase III clinical trials and translated to practice for behavioral cancer prevention. Qualifications: As the Mary W. Calkins Professor of Psychiatry and Deputy Director of the Abramson Cancer Center at UPenn, I have decades of experience conducting innovative behavioral science research that bridges the fields of neuroscience, pharmacology, and genetics. I have been continuously funded by NCI since 1989, with grants totaling ~$67 million in total costs (including an NCI Provocative Question Award). With >345 peer-reviewed publications, my Google Scholar H-INDEX is 90. My service includes membership on the NCI Board of Scientific Advisors, National Human Genome Research Advisory Council, and the National Institutes on Drug Abuse Advisory Council. I am a past President of the Society for Research on Nicotine and Tobacco, and an Elected Member of the Institute of Medicine of the National Academies.




Fine-mapping the CYP2A6 regional association with nicotine metabolism among African American smokers.
Authors: Pouget J.G. , Giratallah H. , Langlois A.W.R. , El-Boraie A. , Lerman C. , Knight J. , Cox L.S. , Nollen N.L. , Ahluwalia J.S. , Benner C. , et al. .
Source: Molecular Psychiatry, 2025 Mar; 30(3), p. 943-953.
EPub date: 2024-08-31 00:00:00.0.
PMID: 39217253
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A structural MRI marker predicts individual differences in impulsivity and classifies patients with behavioral-variant frontotemporal dementia from matched controls.
Authors: Godefroy V. , Durand A. , Simon M.C. , Weber B. , Kable J. , Lerman C. , Bergström F. , Levy R. , Batrancourt B. , Schmidt L. , et al. .
Source: Biorxiv : The Preprint Server For Biology, 2024-09-16 00:00:00.0; , .
EPub date: 2024-09-16 00:00:00.0.
PMID: 39345385
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Multivariate analysis of multimodal brain structure predicts individual differences in risk and intertemporal preference.
Authors: Bergström F. , Schu G. , Lee S. , Lerman C. , Kable J.W. .
Source: Biorxiv : The Preprint Server For Biology, 2024-07-08 00:00:00.0; , .
EPub date: 2024-07-08 00:00:00.0.
PMID: 39026787
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Genetic Prediction of Smoking Cessation Medication Side Effects: A Genome-Wide Investigation of Abnormal Dreams on Varenicline.
Authors: Chenoweth M.J. , Kim Y.J. , Nollen N.L. , Hawk L.W. , Mahoney M.C. , Lerman C. , Knight J. , Tyndale R.F. .
Source: Clinical Pharmacology And Therapeutics, 2024-02-19 00:00:00.0; , .
EPub date: 2024-02-19 00:00:00.0.
PMID: 38369951
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Reduced cortical complexity in ventromedial prefrontal cortex is associated with a greater preference for risky and immediate rewards.
Authors: Bergström F. , Lerman C. , Kable J.W. .
Source: Imaging Neuroscience (cambridge, Mass.), 2024; 2, .
EPub date: 2024-04-18 00:00:00.0.
PMID: 40800479
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Less cortical complexity in ventromedial prefrontal cortex is associated with a greater preference for risky and immediate rewards.
Authors: Bergström F. , Lerman C. , Kable J.W. .
Source: Biorxiv : The Preprint Server For Biology, 2023-09-13 00:00:00.0; , .
EPub date: 2023-09-13 00:00:00.0.
PMID: 37745594
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An fMRI-Based Brain Marker of Individual Differences in Delay Discounting.
Authors: Koban L. , Lee S. , Schelski D.S. , Simon M.C. , Lerman C. , Weber B. , Kable J.W. , Plassmann H. .
Source: The Journal Of Neuroscience : The Official Journal Of The Society For Neuroscience, 2023-03-01 00:00:00.0; 43(9), p. 1600-1613.
EPub date: 2023-01-19 00:00:00.0.
PMID: 36657973
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A neural signature of the vividness of prospective thought is modulated by temporal proximity during intertemporal decision making.
Authors: Lee S. , Parthasarathi T. , Cooper N. , Zauberman G. , Lerman C. , Kable J.W. .
Source: Proceedings Of The National Academy Of Sciences Of The United States Of America, 2022 Nov; 119(44), p. e2214072119.
EPub date: 2022-10-24 00:00:00.0.
PMID: 36279433
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A neural signature of the vividness of prospective thought is modulated by temporal proximity during intertemporal decision making.
Authors: Lee S. , Parthasarathi T. , Cooper N. , Zauberman G. , Lerman C. , Kable J.W. .
Source: Proceedings Of The National Academy Of Sciences Of The United States Of America, 2022 Nov; 119(44), p. e2214072119.
EPub date: 2022-10-24 00:00:00.0.
PMID: 36279433
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Risk-reducing mastectomy decisions among women with mutations in high- and moderate- penetrance breast cancer susceptibility genes.
Authors: Comeaux J.G. , Culver J.O. , Lee J.E. , Dondanville D. , McArthur H.L. , Quinn E. , Gorman N. , Ricker C. , Li M. , Lerman C. .
Source: Molecular Genetics & Genomic Medicine, 2022 10; 10(10), p. e2031.
EPub date: 2022-08-25 00:00:00.0.
PMID: 36054727
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Integration of Universal Germline Genetic Testing for All New Breast Cancer Patients.
Authors: Culver J.O. , Freiberg Y. , Ricker C. , Comeaux J.G. , Chang E.Y. , Banerjee V. , Sturgeon D. , Solomon I. , Kagey J. , Dobre M.G. , et al. .
Source: Annals Of Surgical Oncology, 2022-09-26 00:00:00.0; , .
EPub date: 2022-09-26 00:00:00.0.
PMID: 36161375
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Accuracy and applications of sequencing and genotyping approaches for CYP2A6 and homologous genes.
Authors: Langlois A.W.R. , El-Boraie A. , Fukunaga K. , Mushiroda T. , Kubo M. , Lerman C. , Knight J. , Scherer S.E. , Chenoweth M.J. , Tyndale R.F. .
Source: Pharmacogenetics And Genomics, 2022-02-21 00:00:00.0; , .
EPub date: 2022-02-21 00:00:00.0.
PMID: 35190513
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Functional characterization of novel rare CYP2A6 variants and potential implications for clinical outcomes.
Authors: El-Boraie A. , Tanner J.A. , Zhu A.Z.X. , Claw K.G. , Prasad B. , Schuetz E.G. , Thummel K.E. , Fukunaga K. , Mushiroda T. , Kubo M. , et al. .
Source: Clinical And Translational Science, 2022 01; 15(1), p. 204-220.
EPub date: 2021-09-25 00:00:00.0.
PMID: 34476898
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Analyses of nicotine metabolism biomarker genetics stratified by sex in African and European Americans.
Authors: Chenoweth M.J. , Cox L.S. , Nollen N.L. , Ahluwalia J.S. , Benowitz N.L. , Lerman C. , Knight J. , Tyndale R.F. .
Source: Scientific Reports, 2021-10-01 00:00:00.0; 11(1), p. 19572.
EPub date: 2021-10-01 00:00:00.0.
PMID: 34599228
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Subjective value, not a gridlike code, describes neural activity in ventromedial prefrontal cortex during value-based decision-making.
Authors: Lee S. , Yu L.Q. , Lerman C. , Kable J.W. .
Source: Neuroimage, 2021-08-15 00:00:00.0; 237, p. 118159.
EPub date: 2021-05-12 00:00:00.0.
PMID: 33991700
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Comparing the Rate of Nicotine Metabolism Among Smokers With Current or Past Major Depressive Disorder.
Authors: Schnoll R. , Paul Wileyto E. , Bauer A.M. , Fox E. , Leone F. , Lerman C. , Tyndale R.F. , George T.P. , Hawk L. , Cinciripini P. , et al. .
Source: The American Journal On Addictions, 2021-03-26 00:00:00.0; , .
EPub date: 2021-03-26 00:00:00.0.
PMID: 33772971
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A genome-wide association study of nausea incidence in varenicline-treated cigarette smokers.
Authors: Chenoweth M.J. , Lerman C. , Knight J. , Tyndale R.F. .
Source: Nicotine & Tobacco Research : Official Journal Of The Society For Research On Nicotine And Tobacco, 2021-03-13 00:00:00.0; , .
EPub date: 2021-03-13 00:00:00.0.
PMID: 33713409
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Evidence for racial/ethnic disparities in emergency department visits following breast cancer surgery among women in California: a population-based study.
Authors: Falcone M. , Liu L. , Farias A. , Zhang J. , Kang I. , Li M. , Stern M.C. , Lerman C. .
Source: Breast Cancer Research And Treatment, 2021-03-06 00:00:00.0; , .
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Psychosocial outcomes following germline multigene panel testing in an ethnically and economically diverse cohort of patients.
Authors: Culver J.O. , Ricker C.N. , Bonner J. , Kidd J. , Sturgeon D. , Hodan R. , Kingham K. , Lowstuter K. , Chun N.M. , Lebensohn A.P. , et al. .
Source: Cancer, 2020-12-15 00:00:00.0; , .
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Risk of Persistent Opioid Use following Major Surgery in Matched Samples of Patients with and without Cancer.
Authors: Falcone M. , Luo C. , Chen Y. , Birtwell D. , Cheatle M. , Duan R. , Gabriel P.E. , He L. , Ko E.M. , Lenz H.J. , et al. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2020 Nov; 29(11), p. 2126-2133.
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Flexible Utility Function Approximation via Cubic Bezier Splines.
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Source: Psychometrika, 2020-09-26 00:00:00.0; , .
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Patterns of lapses and recoveries during a quit attempt using varenicline and behavioral counseling among smokers with and without HIV.
Authors: Ashare R.L. , Wileyto E.P. , Logue-Chamberlain E. , Gross R. , Tyndale R.F. , Lerman C. , Hawk L.W. , Cinciripini P. , George T.P. , Lubitz S.F. , et al. .
Source: Psychology Of Addictive Behaviors : Journal Of The Society Of Psychologists In Addictive Behaviors, 2020-07-20 00:00:00.0; , .
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On the evidence consistency of pharmacovigilance outcomes between Food and Drug Administration Adverse Event Reporting System and electronic medical record data for acute mania patients.
Authors: Duan R. , Zhang X. , Du J. , Huang J. , Tao C. , Chen Y. .
Source: Health Informatics Journal, 2020 06; 26(2), p. 753-764.
EPub date: 2019-03-19 00:00:00.0.
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Independent association of tobacco use with opioid use disorder in patients of European ancestry with chronic non-cancer pain.
Authors: Cheatle M.D. , Falcone M. , Dhingra L. , Lerman C. .
Source: Drug And Alcohol Dependence, 2020-04-01 00:00:00.0; 209, p. 107901.
EPub date: 2020-02-14 00:00:00.0.
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Genome-wide association meta-analysis of nicotine metabolism and cigarette consumption measures in smokers of European descent.
Authors: Buchwald J. , Chenoweth M.J. , Palviainen T. , Zhu G. , Benner C. , Gordon S. , Korhonen T. , Ripatti S. , Madden P.A.F. , Lehtimäki T. , et al. .
Source: Molecular Psychiatry, 2020-03-10 00:00:00.0; , .
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The Use of the Nicotine Metabolite Ratio as a Biomarker to Personalize Smoking Cessation Treatment: Current Evidence and Future Directions.
Authors: Siegel S.D. , Lerman C. , Flitter A. , Schnoll R.A. .
Source: Cancer Prevention Research (philadelphia, Pa.), 2020 Mar; 13(3), p. 261-272.
PMID: 32132120
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Impact of Early Nausea on Varenicline Adherence and Smoking Cessation.
Authors: Peng A.R. , Swardfager W. , Benowitz N.L. , Ahluwalia J.S. , Lerman C. , Nollen N.L. , Tyndale R.F. .
Source: Addiction (abingdon, England), 2019-09-10 00:00:00.0; , .
EPub date: 2019-09-10 00:00:00.0.
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Brain Marker Links Stress and Nicotine Abstinence.
Authors: Allenby C. , Falcone M. , Ashare R.L. , Cao W. , Bernardo L. , Wileyto E.P. , Pruessner J. , Loughead J. , Lerman C. .
Source: Nicotine & Tobacco Research : Official Journal Of The Society For Research On Nicotine And Tobacco, 2019-05-22 00:00:00.0; , .
EPub date: 2019-05-22 00:00:00.0.
PMID: 31120113
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Neural cue reactivity during acute abstinence predicts short-term smoking relapse.
Authors: Allenby C. , Falcone M. , Wileyto E.P. , Cao W. , Bernardo L. , Ashare R.L. , Janes A. , Loughead J. , Lerman C. .
Source: Addiction Biology, 2019-02-25 00:00:00.0; , .
EPub date: 2019-02-25 00:00:00.0.
PMID: 30806013
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Lack of effect of transcranial direct current stimulation (tDCS) on short-term smoking cessation: Results of a randomized, sham-controlled clinical trial.
Authors: Falcone M. , Bernardo L. , Wileyto E.P. , Allenby C. , Burke A.M. , Hamilton R. , Cristancho M. , Ashare R.L. , Loughead J. , Lerman C. .
Source: Drug And Alcohol Dependence, 2019-01-01 00:00:00.0; 194, p. 244-251.
EPub date: 2018-11-13 00:00:00.0.
PMID: 30497056
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Got chocolate? Bilateral prefrontal cortex stimulation augments chocolate consumption.
Authors: To C. , Falcone M. , Loughead J. , Logue-Chamberlain E. , Hamilton R. , Kable J. , Lerman C. , Ashare R.L. .
Source: Appetite, 2018-08-29 00:00:00.0; 131, p. 28-35.
EPub date: 2018-08-29 00:00:00.0.
PMID: 30171915
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Leadership Development in Medicine.
Authors: Lerman C. , Jameson J.L. .
Source: The New England Journal Of Medicine, 2018-05-17 00:00:00.0; 378(20), p. 1862-1863.
PMID: 29768144
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Amygdala Functional and Structural Connectivity Predicts Individual Risk Tolerance.
Authors: Jung W.H. , Lee S. , Lerman C. , Kable J.W. .
Source: Neuron, 2018-03-28 00:00:00.0; , .
EPub date: 2018-03-28 00:00:00.0.
PMID: 29628186
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No Effect of Commercial Cognitive Training on Brain Activity, Choice Behavior, or Cognitive Performance.
Authors: Kable J.W. , Caulfield M.K. , Falcone M. , McConnell M. , Bernardo L. , Parthasarathi T. , Cooper N. , Ashare R. , Audrain-McGovern J. , Hornik R. , et al. .
Source: The Journal Of Neuroscience : The Official Journal Of The Society For Neuroscience, 2017-08-02 00:00:00.0; 37(31), p. 7390-7402.
EPub date: 2017-07-10 00:00:00.0.
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Precision Medicine For Tobacco Dependence: Development And Validation Of The Nicotine Metabolite Ratio
Authors: Allenby C.E. , Boylan K.A. , Lerman C. , Falcone M. .
Source: Journal Of Neuroimmune Pharmacology : The Official Journal Of The Society On Neuroimmune Pharmacology, 2016 Sep; 11(3), p. 471-83.
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Nicotine withdrawal alters neural responses to psychosocial stress.
Authors: Ashare R.L. , Lerman C. , Cao W. , Falcone M. , Bernardo L. , Ruparel K. , Hopson R. , Gur R. , Pruessner J.C. , Loughead J. .
Source: Psychopharmacology, 2016 Jul; 233(13), p. 2459-67.
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Transcranial Direct Current Brain Stimulation Increases Ability to Resist Smoking.
Authors: Falcone M. , Bernardo L. , Ashare R.L. , Hamilton R. , Faseyitan O. , McKee S.A. , Loughead J. , Lerman C. .
Source: Brain Stimulation, 2016 Mar-Apr; 9(2), p. 191-6.
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Transcranial direct current brain stimulation decreases impulsivity in ADHD.
Authors: Allenby C. , Falcone M. , Bernardo L. , Wileyto E.P. , Rostain A. , Ramsay J.R. , Lerman C. , Loughead J. .
Source: Brain Stimulation, 2018 Sep - Oct; 11(5), p. 974-981.
EPub date: 2018-04-23 00:00:00.0.
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