Welcome to my brain blob website! Within it, you will find links that will allow you to access brain blobs from recently published papers.

Contact Information:

Teresa Franklin, Ph.D.
Research Associate Professor of Neuroscience in Psychiatry
Center for the Studies of Addiction
Brain and Behavioral Vulnerabilities Laboratory
3535 Market Street, Philadelphia, PA 19104
University of Pennsylvania Perelman School Of Medicine
Email: teresafr@pennmedicine.upenn.edu
http://www.franklinbrainimaging.com
http://www.med.upenn.edu/apps/faculty/index.php/g332/p19076

A Summary of My Research:

My ultimate goal as an Addictions’ Researcher is to characterize pharmaco-responsive endophenotypes in smokers to aid them in achieving successful smoking cessation. There are two major factors that motivate relapse to smoking: a) craving induced by pharmacological withdrawal from nicotine and b) craving elicited by exposure to smoking reminders (smoking cues). Our group was the first to show that smoking cues activate limbic circuitry independent of withdrawal, demonstrating that cues on their own are sufficient to stimulate drug motivated behavior. We hypothesize that there is inter-individual variability in the relative contribution of withdrawal- and smoking cue-induced craving to relapse. We focus on cue-vulnerable subtypes of smokers — and pharmacotherapies that show promise to reduce relapse rates in these subtypes. The tools I am using to identify the subtypes are a) appetitive smoking cue videos in a withdrawal versus sated imaging paradigm, b) the quantitative imaging technique of continuous arterial spin labeled (CASL) perfusion fMRI, c) GABA B agonists such as baclofen, d) the partial nicotinic agonist and FDA-approved smoking cessation agent, varenicline, e) behavioral probes that predict relapse, including attention tasks and affective bias tasks, cigarette consumption and treatment outcome, and g) a candidate gene approach of functional polymorphisms involved in smoking behavior. We have published and replicated our findings showing that genetic variance in the dopamine transporter (DAT) modulates brain and behavioral responses during smoking cue exposure. We are currently exploring the interaction between the DAT and other dopaminergic regulating molecules, which have been shown to be involved in reward and smoking cue responsivity.

Further exploration into the characterization of phenotypes in smokers includes the study of sex and menstrual cycle influences on smoking behavior. Mostly empirical evidence suggests that female smoking behavior is motivated more by the sensory aspects of smoking while the contribution to continued smoking in males is influenced more by the maintenance of nicotine levels in the brain (withdrawal). In our examination of smoking cue responsivity between males and females we observed that males had greater responses during smoking cue exposure compared to females. Given this finding was opposite to our original hypothesis we are continuing to probe our findings by examining resting baseline and functional connectivity differences between males and females.We have also shown that menstrual cycle phase influences smoking cue responsivity and treatment outcome: luteal females (females in the premenstrual phase of their cycle) have greater subjective craving elicited by smoking cue exposure compared to follicular females. Further, we demonstrated that premenopausal females who begin treatment in the follicular phase, and are simultaneously protected from withdrawal have at least a 70% chance of success in smoking cessation compared to a 20% success rate in females who begin treatment in the luteal phase.The action of varenicline to increase activity in the reward-evaluating lateral orbitofrontal cortex predicts its actions to reduce activity in the reward-responsive ventral striatum/medial orbitofrontal cortex.

In other studies, we have data showing that both marijuana cues and smoking cues activate the same reward-related brain circuitry, suggesting similar brain vulnerabilities, and further, that medications that might aid smokers may also aid marijuana-dependent cigarette smokers. We have also shown that cocaine cues and marijuana cues presented for 33 msec activate limbic circuitry and correlate with craving and years of use. Although coping with conscious triggers may be effective for some individuals, it is possible that the brain's response to reward cues may begin outside conscious awareness and, consequently, may not be amenable to existing cognitive treatment approaches. Activation of reward neurocircuitry may provoke craving and perhaps prime an individual for subsequent drug motivated behaviors.

Evidence suggests that an anxiety-prone cue-vulnerable subtype will respond to baclofen, which we have shown has efficacy in a cigarette smoking reduction study, and blunts both brain activity in reward-related neural activity in the brain in ‘at rest’ and during smoking cue exposure. Because of the similar brain signature, and possibly similar brain vulnerabilities, we are currently acquiring data to examine the brain and behavioral effects of baclofen on marijuana smokers who also smoke cigarettes.

Additional studies include the use of the imaging technique, single photon emission computed tomography (SPECT), and the DAT-specific radiotracer, TRODAT to examine whether the DAT-mediated effects on smoking cue reactivity are due to less available or less functional DATs.

Ultimately, the goal for contemporary medicine is to establish brain/behavioral/genetic endophenotypes of medication response, so that treatment strategies can be tailored to manage individual vulnerabilities to aid in conquering addiction.


Click on the article titles below to see brain data in all three planes for each publication.

Brain substrates of early (4 h) cigarette abstinence: Identifcation of treatment targets

2017 Drug and Alcohol Dependence

Elsevier Link
Multi-site exploration of sex differences in brain reactivity to smoking cues: Consensus across sites and methodologies

2017 Drug and Alcohol Dependence

Science Direct link
Early versus late onset of cannabis use: Differences in striatal response to cannabis cues

2016 Cannabis and Cannabinoid Research

PubMed link
Limitations of the use of the MP-RAGE to identify neural changes in the brain: Recent cigarette smoking alters gray matter indices in the striatum

2015 Frontiers in Human Neuroscience

PubMed link
The effects of chronic cigarette smoking on gray matter volume: Influence of sex

PLOS One

PLOS One link
Sex Differences in Resting State Neural Networks of Nicotine-Dependent Cigarette Smokers

2014 Addictive Behaviors

Science Direct link
Neural responses to subliminally presented cannabis and other emotionally evocative cues in cannabis-dependent individuals

2013 Psychopharmacology

PubMed link
Reward-related brain response and craving correlates of marijuana cue exposure: A preliminary study in treatment-seeking marijuana-dependent subjects

2013 Journal of Addiction Medicine

PubMed link
The impact of sex on brain responses to smoking cues: a perfusion fMRI study

2013 Biology of Sex Differences

Biology of Sex Differences link
Acute baclofen diminishes resting baseline blood flow to limbic structures: A perfusion fMRI study

2012 Drug and Alcohol Dependence

PubMed link
A VBM study demonstrating ‘apparent’ effects of a single dose of medication on T1-weighted MRIs

2012 Brain Structure and Function

PubMed link
Neural correlates of attentional bias for smoking cues: modulation by variance in the dopamine transporter gene

2012 Addiction Biology

PubMed link
Effects of varenicline on smoking cue–triggered neural and craving responses

2011 Archives of General Psychiatry

PubMed link
Dopamine transporter genotype modulation of neural responses to smoking cues: Confirmation in a new cohort

2011 Addiction Biology

PubMed link
Modulation of resting brain cerebral blood flow by the GABA B agonist, baclofen: A longitudinal perfusion fMRI study

2011 Drug and Alcohol Dependence

PubMed link

Articles

Emotional, physical and sexual abuse are associated with a heightened limbic response to cocaine cues

2016 Addiction Biology

Ovarian Hormones, Menstrual Cycle Phase, and Smoking: a Review with Recommendations for Future Studies

2016 Current Addiction Reports

Gram Years: A Method to Standardize and Quantify Lifetime Cannabis Consumption

2016 Cannabis and Cannabinod Research

Influence of menstrual cycle phase on resting-state functional connectivity in naturally cycling, cigarette-dependent women

2016 Biology of Sex Differences

Sex Differences in Associations Between Cannabis Craving and Neural Responses to Cannabis Cues: Implications for Treatment

2015 Experimental and Clinical Psychopharmacology

Brief report: “Spiders-No, Puppies-Go”, introducing a novel Go NoGo task tested in inner city adolescents at risk for poor impulse control

2015 Journal of Adolescence

Cannabis, cigarettes, and their co-occurring use: Disentangling differences in default mode network functional connectivity

2015 Drug and Alcohol Dependence

Influence of Menstrual Cycle Phase on Neural and Craving Responses to Appetitive Smoking Cues in Naturally Cycling Females

2015 Nicotine & Tobacco Research

Cannabis, Cigarettes, and Their Co-Occurring Use: Disentangling Differences in Gray Matter Volume

2015 International Journal of Neuropsychopharmacology

Nipping Cue Reactivity in the Bud: Baclofen Prevents Limbic Activation Elicited by Subliminal Drug Cues

2014 The Journal of Neuroscience

The Effects of Chronic Cigarette Smoking on Gray Matter Volume: Influence of Sex

2014 PLOS One

A VBM study demonstrating ‘apparent’ effects of a single dose of medication on T1-weighted MRIs

2012 Brain Structure and Function

Wavelet-transformed temporal cerebral blood flow signals during attempted inhibition of cue-induced cocaine craving distinguish prognostic phenotypes

2012 Drug and Alcohol Dependence

Effects of Varenicline on Smoking Cue–Triggered Neural and Craving Responses

2011 Archives of General Psychiatry

Dopamine transporter genotype modulation of neural responses to smoking cues: confirmation in a new cohort

2011 Addiction Biology

DAT Genotype Modulates Brain and Behavioral Responses Elicited by Cigarette Cues

2009 Neuropsychopharmacology

The GABA B agonist baclofen reduces cigarette consumption in a preliminary double-blind placebo-controlled smoking reduction study

2009 Drug and Alcohol Dependence

Prelude to Passion: Limbic Activation by ‘‘Unseen’’ Drug and Sexual Cues

2008 PLOS One

Menstrual Cycle Phase at Quit Date Predicts Smoking Status in an NRT Treatment Trial: A Retrospective Analysis

2008 Journal of Women's Health

Limbic Activation to Cigarette Smoking Cues Independent of Nicotine Withdrawal: A Perfusion fMRI Study

2007 Neuropsychopharmacology

Conceptual, methodological, and analytical issues in the study of relapse

2006 Clinical Psychology Review

Retrospective study: Influence of menstrual cycle on cue-induced cigarette craving

2004 Nicotine & Tobacco Research

Decreased Gray Matter Concentration in the Insular, Orbitofrontal, Cingulate, and Temporal Cortices of Cocaine Patients

2002 Society of Biological Psychiatry

The retrograde tracer fluoro-gold interferes with the expression of fos-related antigens

2000 Journal of Neuroscience Methods

Expression of Fos-related antigens in the nucleus accumbens and associated regions following exposure to a cocaine-paired environment

2000 European Journal of Neuroscience

Involvement of the Nucleus Accumbens and Medial Prefrontal Cortex in the Expression of Conditioned Hyperactivity to a CocaineAssociated Environment in Rats

2000 Neuropsychopharmacology