Perelman School of Medicine at the University of Pennsylvania

The Center for Interdisciplinary Research on Nicotine Addiction

CIRNA

Brain and Behavior Change Program


Vision and Goals

There is a new opportunity to translate concepts and tools from the field of cognitive neuroscience to accelerate the science and practice of health behavior change interventions. With advances in the neuroimaging field, we are learning where and how self-control processes are executed in the brain. This work points to the central role of neural activity in the dorsolateral prefrontal cortices in self-control processes that contribute to healthy choices.  Further, emerging evidence shows that activity in the prefrontal cortices and cognitive control circuits can be modulated using a variety of strategies including cognitive exercise training, pharmacotherapy, direct current transcranial stimulation, and neuro-feedback training.

The Brain and Behavior Change Program within the Center for Interdisciplinary Research for Nicotine Addiction will translate cognitive neuroscience research into clinical interventions to motivate and sustain health behavior change. The main premise is that it is possible to enhance the brain’s capacity to activate cognitive control circuits to modulate self-control processes that contribute to health risk behaviors, and ultimately to poor health outcomes. 

Program Team

♦  Caryn Lerman, Ph.D. 

♦  James Loughead, Ph.D.

♦  Janet Audrain-McGovern, Ph.D. 

♦  Mary Falcone, Ph.D.

♦  Joseph Kable, Ph.D.

♦  Roy Hamilton, Ph.D.  

 

Project Descriptions

Working memory-related neural activity predicts future smoking relapse 

Brief abstinence from smoking impairs cognition, particularly executive function, and this has a role in relapse to smoking. This study examined whether working memory-related brain activity predicts subsequent smoking relapse above and beyond standard clinical and behavioral measures. Eighty treatment-seeking smokers completed two functional magnetic resonance imaging sessions (smoking satiety vs 24 h abstinence challenge) during performance of a visual N-back task. Brief counseling and a short-term quit attempt followed. Relapse during the first 7 days was biochemically confirmed by the presence of the nicotine metabolite cotinine. Mean percent blood oxygen level-dependent (BOLD) signal change was extracted from a priori regions of interest: bilateral dorsolateral prefrontal cortex (DLPFC), medial frontal/cingulate gyrus, posterior cingulate cortex (PCC), and ventromedial prefrontal cortex. Signal from these brain regions and additional clinical measures were used to model outcome status, which was then validated with resampling techniques. Relapse to smoking was predicted by increased withdrawal symptoms, decreased left DLPFC and increased PCC BOLD percent signal change (abstinence vs smoking satiety). Receiver operating characteristic analysis demonstrated 81% area under the curve using these predictors, a significant improvement over the model with clinical variables only. The combination of abstinence-induced decreases in left DLPFC activation and reduced suppression of PCC may be a prognostic marker for poor outcome, specifically early smoking relapse.

Resisting Smoking and Direct Current Transcranial Stimulation (tDCS)

Behaviors such as tobacco use, unhealthy diet, and sedentary behavior have far-reaching health implications.  These modifiable behaviors account for a substantial proportion of deaths from cancer, cardiovascular disease and diabetes, and take a significant economic toll. Yet, many unhealthy behaviors are very resistant to change, despite widespread knowledge of the risks. Although theories of behavior change have been advanced to explain the persistence of these behaviors, few consider the neurobehavioral underpinnings. These approaches also fail to address a fundamental aspect of behavior change – an individual’s ability to exert sufficient self-control to overcome temptations for immediate gratification and/or to maintain attention to long-term goals. With advances in the neuroimaging field, we are learning where and how self-control over decisions and behaviors is executed in the brain. This work points to the central role of neural activity in the dorsolateral prefrontal cortices (DLPFC) in self-control processes that contribute to healthy choices.  Further, emerging evidence shows that activity in the prefrontal cortices and cognitive control circuits can be modulated using a noninvasive and safe intervention: tDCS.  This within-subject proof of concept study will investigate whether one session of tDCS (versus sham stimulation) can reduce smoking cue-induced craving and increase the ability to resist smoking.  

ADHD and Direct Current Transcranial Stimulation (tDCS) Pilot

Attention Deficit Hyperactivity Disorder (ADHD) is characterized by symptoms of impulsivity, inattention, and hyperactivity that emerge in childhood and frequently persist into adulthood. These symptoms are accompanied by deficits in cognitive control and risky decision making that can lead to negative psychosocial and health-related outcomes. With advances in the neuroimaging field, we are learning where and how self-control over decisions and behaviors is executed in the brain. This work points to the central role of neural activity in the dorsolateral prefrontal cortices (DLPFC) in self-control processes that contribute to healthy choices.  Further, emerging evidence shows that activity in the prefrontal cortices and cognitive control circuits can be modulated using a noninvasive and safe intervention: tDCS. This between-subject proof of concept study will investigate whether one session of 1milliamp (mA) or 2mA tDCS (versus sham stimulation) can enhance executive cognitive function in adults; we will also investigate the dose-response relationship to identify the optimal tDCS dosage for improving cognitive function in ADHD.

Retraining Cognitive Functioning 

Health risk behaviors, such as tobacco and alcohol consumption, unhealthy diet, and physical inactivity have far-reaching implications for cancer prevention. More than 1 in 4 young adults report having used tobacco in the past month. Roughly 42% of young adults are overweight, with 16% meeting the criterion for obesity. Young adulthood is a critical period for establishing lifestyle behaviors that persist into adulthood. These modifiable behaviors account for over 60% of cancer deaths, and have a significant economic toll. Emerging work in behavioral economics and cognitive neuroscience suggests a novel strategy to shift behavioral choices toward healthy long-term goals. The proposed study will: (a) evaluate the efficacy of a neurocognitive training intervention (CT) for improving responses to measures of decision-making that relate to impulsive behaviors: delay discounting and risk sensitivity; and (b)  use functional MRI to test whether changes in neural activity mediate effects on behavior. One hundred and seventy-six healthy participants between the ages of 18 and 35 will be randomly assigned to one of two conditions: (a) web-based cognitive exercises (cognitive training; CT) designed to improve attention, working memory, response inhibition and overall executive function or (b) web-based game-like activities to control for cognitive stimulation (cognitive stimulation; CS). Both conditions will undergo an fMRI at baseline (before intervention) and after the 10-week intervention has concluded to test the effect of CT on decision making. Primary outcomes include changes in BOLD signal outcomes and decision making tasks (discount rate and risk sensitivity). Intermediate outcomes include changes in cognitive performance, such as attention, working memory, and response inhibition.

 

Active Grants

Neuroscience-Based Interventions for Cancer Risk Behavior     (08/01/15 - 07/30/22)

UPENN TCORS: Tobacco Product Messaging in a Complex Communication Environment     (09/01/13 - 08/31/18)

Retraining Neurocognitive Mechanisms of Cancer Risk Behavior     (07/01/12 - 06/30/16)

Cognitive Training for Nicotine Dependence     (09/30/10 - 06/30/15) *No Cost Extension*

 

Selected Publications

Loughead J, Wileyto EP, Valdez JN , Sanborn P, Tang K, Strasser AA, Ruparel K, Ray R, Gur RC, Lerman C.  Effect of abstinence challenge on brain function and cognition in smokers differs by COMT genotype.  Molecular Psychiatry, 2009; 14(8):820-826 (PMID19065145; PMCID3896978).

Loughead J, Ray R, Wileyto EP, Ruparel K, Sanborn P, Siegel S, Gur RC, Lerman C.  Effects of the a4b2 partial agonist varenicline on brain activity and working memory in abstinent smokers.  Biological Psychiatry, 2010; 67(8):715-721 (PMID20207347; PMCID in Process).

Ashare R, Valdez J, Ruparel K, Albelda B, Hopson R, Keefe J, Loughead J, Lerman C.  Association of abstinence-induced alterations in working memory function and COMT genotype in smokers.  Psychopharmacology, 2013; 230(4):653-662 (PMID23828159; PMC3840089).

Ashare RL, Wileyto EP, Ruparel K, Goelz PM, Hopson RD, Valdez JN, Gur RC, Loughead J, Lerman C.  Effects of tolcapone on working memory and brain activity in abstinent smokers:  A proof-of-concept study.  Drug and Alcohol Dependence, 2013; 133(3):852-856 (PMID24095246; PMCID3814299).

Lerman C, Gu H, Loughead J, Ruparel K, Yang Y, Stein EA. Large scale brain network coupling predicts acute nicotine abstinence effects on craving and cognitive function. JAMA Psychiatry, 2014; 71(5):523-530 (PMID24622915; PMCID4097018).

Loughead J, Wileyto EP, Ruparel K, Falcone M, Hopson R, Gur R, Lerman C.  Working memory-related neural activity predicts future smoking relapse. Neuropsychopharmacology, 2015, 40(6):1311-1320 (PMID25469682; PMCID4397393).

 

Press

Philadelphia Inquirer Article; 2015: Could changing the brain help smokers quit?

Philadelphia Inquirer Article; 2015: New brain-imaging approach could help smokers quit

Philadelphia Inquirer Article; 2015: Can brain games change behaviors long term?