Neuromodulation of Decision-Making in the Addictive Brain

Abstract

Noninvasive brain stimulation of the dorsolateral prefrontal cortex with repetitive transcranial magnetic stimulation and transcranial direct current stimulation can modify decision-making behaviors in healthy subjects. The same type of noninvasive brain stimulation can suppress drug craving in substance user patients, who often display impaired decision-making behaviors. We discuss the implications of these studies for the cognitive neurosciences and their translational applications to the treatment of addictions. We propose a neurocognitive model that can account for our findings and suggests a promising therapeutic role of brain stimulation in the treatment of substance abuse and addictive behavior disorders.

Keywords :

• addiction
• craving
• decision-making
• neurocognition
• dorsolateral prefrontal cortex
• transcranial magnetic stimulation
• transcranial direct current stimulation

THE AUTHORS

Shirley Fecteau, PhD, is an Instructor of Neurology at Harvard Medical School and a member of the Berenson-Allen Center for Noninvasive Brain Stimulation at Beth Israel Deaconess Medical Center. She was awarded a CIHR fellowship (first percentile). Her research aims at promoting cognitive functions and behaviors related to the prefrontal cortex in neurological and psychiatric populations. In order to achieve this, she has been characterizing and modulating brain plasticity related to prefrontal functions in healthy individuals and patients using neuromodulation and neuroimaging techniques and real-time combination of these techniques. The motivation behind her work is to provide proof-of-concept studies suggesting potential improvement of cognitive functions and behaviors that may ultimately lead to beneficial interventions for clinical populations.

Felipe Fregni, MD, PhD, MPH, is an Assistant Professor of Neurology at Harvard Medical School, the Director of Clinical Trials Network at the Berenson-Allen Center for Noninvasive Brain Stimulation at Beth Israel Deaconess Medical Center, and the Director of the Continuing Education for Scholars in Clinical Science Program at Harvard Medical School.

Paulo S. Boggio, PhD, is an Adjunct Professor at Mackenzie Presbyterian University, Sao Paulo, Brazil. He is the Director of Research at the Center for Health and Biological Sciences at Mackenzie Presbyterian University and Director of the Cognitive Neuroscience Laboratory at the same institution.

Joan A. Camprodon, PhD, was born in Barcelona (Spain) and studied Medicine at the University of Barcelona and the Humboldt University in Berlin. He did a PhD in Neuroscience with Alvaro Pascual-Leone and a Master in Public Health at the Harvard School of Public Health. He obtained his first faculty appointment as Instructor of Neurology at Harvard Medical School and continued working at the Berenson-Allen Center for Noninvasive Brain Stimulation. He is currently a resident physician and researcher at the Department of Psychiatry of the Massachusetts General Hospital. His research focuses on the study of neural connectivity and plasticity in health and disease. He uses TMS, fMRI, and the simultaneous combination of both to study dynamic neural networks and their properties in the context of systems and cognitive neuroscience. He also works on the application of these paradigms and methods to patient-oriented questions in Translational Neuropsychiatry. This latter research particularly focuses on combining neuroimaging with neurostimulation to study the role of plasticity in the pathophysiology of neuropsychiatric disorders such as addictions, depression or neglect, and explore the therapeutic potential of neuromodulation. His clinical interests are in neuropsychiatry and behavioral neurology, at the interface between psychiatry, neurology, and medicine.

Alvaro Pascual-Leone is a Professor of Neurology and Director of the Berenson-Allen Center for Noninvasive Brain Stimulation at Beth Israel Deaconess Medical Center and Harvard Medical School, where he also serves as Program Director of the Harvard-Thorndike Clinical Research Center. He has authored over 350 scientific papers and is the recipient of several international honors and awards, including the Ramon y Cajal Award in Neuroscience (Spain), the Norman Geschwind Prize in Behavioral Neurology from the American Academy of Neurology, the Friedrich Wilhelm Bessel Research Award from The Alexander von Humboldt Foundation (Germany), and the Jean Signoret Prize from the Ipsen Foundation (France). His research aims at understanding the mechanisms that control brain plasticity across the lifespan to be able to modify them for the subjects’ optimal behavioral outcome. Pascual-Leone combines various brain imaging and brain stimulation methodologies to establish a causal relationship and a precise chronometry between regional brain activation and behavior, and uses noninvasive brain stimulation techniques to modulate brain plasticity, suppressing some changes and enhancing others, to gain a clinical benefit and behavioral advantage for a given individual. Such noninvasive approaches can lead to clinically relevant therapeutic effects in neuropsychiatry and neurorehabilitation, and serve as proof-of-principle prior to more invasive neuromodulatory interventions.

Notes

1 In the Risk Task, subjects are presented with six horizontally arranged boxes that could be pink or blue. The ration of pink and blue boxes varies from trial to trial and can be 5:1, 4:2, or 3:3. Participants have to pick the color of the box that hides the winning token. They are told that the token is equally likely to be hidden in any of the boxes. Therefore, for each trial, the ratio of pink to blue boxes (referred to as level of risk) effectively determines the probability of finding the winning token and thus the level of risk of the choice. Participants are rewarded with points for correctly guessing the color of the box hiding the winning token and punished by losing points for picking the incorrect color. The amount of reward (or penalty) points associated with any scenario varies and is clearly indicated on the computer screen. Here, the conflict inherent in risk taking is reflected by the fact that the largest reward is always associated with the least likely of the two outcomes (i.e., the most risky option).

2 In the Ultimatum Game, a proposer (here the investigator) offers the subject to split a certain amount of money. The subject can either accept or reject the offer. If he or she accepts the offer, the money is split as proposed, but if he or she rejects, none of them receive the money.

3 In the BART, subjects have to make a choice in a context of increasing risk. They are invited to inflate a computerized balloon by pushing a “pump.” The balloon can explode at any moment. Participants have to decide after each pump whether to keep pumping and risk explosion of the balloon, or to stop. Subjects accumulate money in a temporary bank with each pump (e.g., 5 cents for each pump). When the subject decides to stop pumping, the accumulated money is transferred to a permanent bank. However, if the balloon explodes, all of the money accumulated in the temporary bank is lost. Therefore, the probability of losing the money, as well as the potential loss (i.e., the amount of money), increases with each pump.