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Cognition and Addiction
A Researcher’s Guide from Mechanisms
Towards Interventions

Edited by
Antonio Verdejo-Garcia
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 I have been dedicated to edit this book during the last couple of years, but the
knowledge and collaborations that have made it possible span over 15 years.
Thus, I would like to dedicate this book to my mentors: Professors Miguel
Perez-Garcı́a, Antoine Bechara, and Karen Bolla and to the many colleagues and
friends (and colleagues who became friends) with whom I have shared amazing
research and life adventures in Granada, Barcelona, Iowa, Baltimore, Cambridge,
and Melbourne. To my parents, for fighting to give me a university education and
teaching me to always decide by myself. Huge thanks to my wife, Natalia, for
being an inspiration and spring of energy for so many personal and career
choicesdI look up to you every single day.
Antonio Verdejo-Garcı́a,
Melbourne, May 2019
Contributors
Merideth A. Addicott, Department of Psychiatry, Uni-
versity of Arkansas for Medical Science, Little Rock,
AR, United States
Robin L. Aupperle, Laureate Institute for Brain Research,
Tulsa, OK, United States
Alex Baldacchino, Division of Populations and Health
Science, St Andrews Medical School, University of
St Andrews, St Andrews, Fife, United Kingdom
Joël Billieux, Addictive and Compulsive Behaviours
Laboratory, Institute for Health and Behaviours, Uni-
versity of Luxembourg, Esch-sur-Alzette, Luxembourg
Marilisa Boffo, Addiction Development and Psychopathol-
ogy (ADAPT) Laboratory, Department of Psychology,
University of Amsterdam, Amsterdam, The Netherlands;
Department of Psychology, Education and Child
Studies, Erasmus University Rotterdam, Rotterdam,
The Netherlands
Matthias Brand, General Psychology: Cognition and
Center for Behavioral Addiction Research (CeBAR),
University of Duisburg-Essen, Duisburg, Germany;
Erwin L. Hahn Institute for Magnetic Resonance Imaging,
Essen, Germany
Damien Brevers, Laboratory of Psychological Medicine
and Addictology, Faculty of Medicine, Brugmann-
Campus, Université Libre de Bruxelles, Brussels,
Belgium; Research in Psychology Applied to Motor
Learning, Faculty of Motor Sciences, Erasme Campus,
Université Libre de Bruxelles, Brussels, Belgium
Gabriel Brooks, Centre for Gambling Research at UBC,
Department of Psychology, University of British
Columbia, Vancouver, BC, Canada
S.J. Brooks, School of Natural Sciences and Psychology,
Liverpool John Moores University, Liverpool, United
Kingdom; Department of Neuroscience, Uppsala Uni-
versity, Uppsala, Sweden
M. Aryana Bryan, Center on Mindfulness and Integrative
Health Intervention Development, University of Utah,
Salt Lake City, UT, United States
Nicolas Cabé, Normandie Univ, UNICAEN, PSL Uni-
versité de Paris, EPHE, INSERM, U1077, CHU de
Caen, GIP Cyceron, Neuropsychologie et Imagerie de la
Mémoire Humaine, Caen, France
Zhipeng Cao, School of Psychology, University College
Dublin, Dublin, Ireland
Adrian Carter, Turner Institute for Brain and Mental
Health, Monash University, Melbourne, VIC, Australia;
UQ Centre for Clinical Research, University of
Queensland, Brisbane, QLD, Australia
Natalie Castellanos-Ryan, Universite de Montreal, CHU
Ste Justine, Montreal, QC, Canada
Luke Clark, Centre for Gambling Research at UBC,
Department of Psychology, University of British
Columbia, Vancouver, BC, Canada
Patricia Conrod, Universite de Montreal, CHU Ste Jus-
tine, Montreal, QC, Canada
Fleur Davey, Research and Development Department,
NHS Fife, Dunfermline, Fife, United Kingdom
Andrew Dawson, Turner Institute for Brain and Mental
Health, Monash University, Melbourne, VIC, Australia
Logan T. Dowdle, Department of Psychiatry and Behav-
ioral Sciences, College of Medicine, Medical University
of South Carolina. Charleston, SC, United States
Timothy C. Durazzo, Stanford University and Palo Alto
VA Medical Center, Stanford, CA, United States
Hamed Ekhtiari, Laureate Institute for Brain Research,
Tulsa, OK, United States
Mario Ferrari, Centre for Gambling Research at UBC,
Department of Psychology, University of British
Columbia, Vancouver, BC, Canada
Matt Field, Department of Psychology, University of
Sheffield, Sheffield, South Yorkshire, United Kingdom
S. Funk, Department of Psychology, University of Cape
Town, Cape Town, South Africa
xv
xvi Contributors
Gloria Garcia-Fernandez, School of Psychological
Sciences and Turner Institute for Brain and Mental
Health, Monash University, Melbourne, VIC, Aus-
tralia; Faculty of Psychology, University of Oviedo,
Oviedo, Spain
Eric L. Garland, Center on Mindfulness and Integrative
Health Intervention Development, University of Utah,
Salt Lake City, UT, United States
Rita Z. Goldstein, Departments of Psychiatry and Neuro-
science, Icahn School of Medicine at Mount Sinai, New
York, NY, United States
Raul Gonzalez, Center for Children and Families,
Department of Psychology, Florida International Uni-
versity, Miami, FL, United States
Renee D. Goodwin, Department of Epidemiology and
Biostatistics, School of Public Health, The City Uni-
versity of New York, New York, NY, United States;
Department of Epidemiology, Mailman School of
Public Health, Columbia University, New York, NY,
United States
Anna E. Goudriaan, Amsterdam UMC, Department of
Psychiatry, University of Amsterdam, the Netherlands;
Amsterdam Institute for Addiction Research; Arkin
Mental Health; Department of Quality of Care and
Research and Jellinek, Amsterdam, The Netherlands
Wayne Hall, UQ Centre for Clinical Research, University
of Queensland, Brisbane, QLD, Australia; Centre for
Youth Substance Abuse Research, University of
Queensland, Brisbane, QLD, Australia; National
Addiction Centre, Kings College London, London,
WC2R 2LS, United Kingdom
Adam W. Hanley, Center on Mindfulness and Integrative
Health Intervention Development, University of Utah,
Salt Lake City, UT, United States
Colleen A. Hanlon, Department of Psychiatry and
Behavioral Sciences, College of Medicine, Medical
University of South Carolina, Charleston, SC, United
States
Matthew O. Howard, University of North Carolina at
Chapel Hill, Chapel Hill, NC, United States
Andrew Jones, Department of Psychological Sciences,
University of Liverpool, Liverpool, Merseyside, United
Kingdom
Daniel L. King, School of Psychology, The University of
Adelaide, Adelaide, SA, Australia; College of Educa-
tion, Psychology and Social Work, Flinders University,
Adelaide, SA, Australia
Jacob W. Koudys, University of Toronto, Toronto, ON,
Canada
Daniel H. Lench, Department of Psychiatry and Behavioral
Sciences, College of Medicine, Medical University of
South Carolina. Charleston, SC, United States
Angéline Maillard, Normandie Univ, UNICAEN, PSL
Université de Paris, EPHE, INSERM, U1077, CHU de
Caen, GIP Cyceron, Neuropsychologie et Imagerie de la
Mémoire Humaine, Caen, France
Pierre Maurage, Laboratory for Experimental Psychopa-
thology, Psychological Science Research Institute,
Université Catholique de Louvain, Louvain-la-Neuve,
Belgium
Dieter J. Meyerhoff, University of California San Fran-
cisco and San Francisco VA Medical Center, San
Francisco, CA, United States
Scott J. Moeller, Department of Psychiatry, Stony Brook
University School of Medicine, Stony Brook, NY,
United States
Catharine Montgomery, School of Natural Sciences and
Psychology, Liverpool John Moores University,
Liverpool, United Kingdom
Laura O’Halloran, School of Psychology, Trinity College
Dublin, Dublin, Ireland
Ileana Pacheco-Colón, Center for Children and Families,
Department of Psychology, Florida International Uni-
versity, Miami, FL, United States
Martin P. Paulus, Laureate Institute for Brain Research,
Tulsa, OK, United States
Tomás Paus, Bloorview Research Institute, Holland
Bloorview Kids Rehabilitation Hospital, Toronto, ON,
Canada; Departments of Psychology and Psychiatry,
University of Toronto, Toronto, ON, Canada
MacKenzie R. Peltier, Yale School of Medicine, Depart-
ment of Psychiatry, New Haven, CT, United States; VA
Connecticut Healthcare System, West Haven, CT, United
States
Brian Pennie, School of Psychology, Trinity College
Dublin, Dublin, Ireland
Anne Lise Pitel, Normandie Univ, UNICAEN, PSL Uni-
versité de Paris, EPHE, INSERM, U1077, CHU de
Caen, GIP Cyceron, Neuropsychologie et Imagerie de la
Mémoire Humaine, Caen, France
Marc N. Potenza, Departments of Psychiatry and Neuro-
science and Child Study Center, Yale School of Med-
icine, New Haven, CT, United States; The Connecticut
Council on Problem Gambling, Wethersfield, CT,
United States; The Connecticut Mental Health Center,
New Haven, CT, United States

Boris B. Quednow, Experimental and Clinical Pharma-
copsychology, Department of Psychiatry, Psychotherapy
and Psychosomatics, Psychiatric Hospital, University of
Zurich, Zurich, Switzerland; Neuroscience Centre
Zurich, University of Zurich and Swiss Federal Institute
of Technology (ETH) Zurich, Zurich, Switzerland
C. Rabier, Department of Psychology, University of Cape
Town, Cape Town, South Africa
Kavya Raj, Turner Institute for Brain and Mental Health,
Monash University, Melbourne, VIC, Australia
Tonisha Kearney Ramos, Department of Psychiatry and
Behavioral Sciences, College of Medicine, Medical
University of South Carolina, Charleston, SC, United
States
Tara Rezapour, Institute for Cognitive Science Studies,
Tehran, Iran; Iranian National Center for Addiction
Studies, Tehran University of Medical Sciences,
Tehran, Iran
Carl A. Roberts, Institute of Psychology, Health and
Society, University of Liverpool, Liverpool, United
Kingdom
Adam J. Rubenis, Turning Point Alcohol and Drug
Centre, Melbourne, VIC, Australia
Anthony C. Ruocco, University of Toronto, Toronto, ON,
Canada
H.B. Schiöth, Department of Neuroscience, Uppsala
University, Uppsala, Sweden
Ryan Smith, Laureate Institute for Brain Research, Tulsa,
OK, United States
Mehmet Sofuoglu, Yale School of Medicine, Department
of Psychiatry, New Haven, CT, United States; VA
Connecticut Healthcare System, West Haven, CT,
United States
Contributors xvii
Douglas Steele, Institute of Neuroscience, Ninewells
Hospital Medical School, University of Dundee,
Dundee, Tayside, United Kingdom
Ryan M. Sullivan, Department of Psychiatry, Stony Brook
University School of Medicine, Stony Brook, NY,
United States; Department of Psychology, University of
Wisconsin-Milwaukee, Milwaukee, WI, United States
Serenella Tolomeo, Division of Populations and Health
Science, St Andrews Medical School, University of St
Andrews, St Andrews, Fife, United Kingdom
Tess den Uyl, Addiction Development and Psychopathol-
ogy (ADAPT) Laboratory, Department of Psychology,
University of Amsterdam, Amsterdam, The Netherlands
Alireza Valyan, Allameh Tabataba’i University, Tehran,
Iran
Antonio Verdejo-Garcia, School of Psychological Sci-
ences and Turner Institute for Brain and Mental Health,
Monash University, Melbourne, VIC, Australia
Fausto Viader, Normandie Univ, UNICAEN, PSL Uni-
versité de Paris, EPHE, INSERM, U1077, CHU de
Caen, GIP Cyceron, Neuropsychologie et Imagerie de la
Mémoire Humaine, Caen, France
Robert Whelan, School of Psychology, Trinity College
Dublin, Dublin, Ireland
Reinout W. Wiers, Addiction Development and Psychopa-
thology (ADAPT) Laboratory, Department of Psychology,
University of Amsterdam, Amsterdam, The Netherlands
Oulmann Zerhouni, UFR Sciences Psychologiques et
Sciences de l’Éducation (SPSE), Université Paris Nan-
terre, Nanterre, France
Anna Zilverstand, Department of Psychiatry, University
of Minnesota, Minneapolis, MN, United States
Biographies
Antonio Verdejo-García has a PhD in Psychology
(Addiction Neuropsychology, University of Granada,
2006) and a Masters in Psychological and Biomedical
Aspects of Health and Illness (University of Granada,
2002). After his PhD, he continued specialized training
in addiction neuroscience in highly prestigious research
centers: Johns Hopkins Medical Institute (Neurology),
IMIM-Hospital del Mar (Pharmacology) and the University
of Cambridge (Behavioural and Clinical Neuroscience
Institute).
Currently, Antonio Verdejo-García is an Australian
Medical Research Future Fund Fellow and holds a Full
ProfessoreResearch appointment at the Turner Institute for
Brain and Mental Health (Monash University), where he is
the Deputy Lead of the Addiction and Mental Health
Program. He also holds honorary appointments at Turning
Point, Australia’s leading national addiction treatment and
research center, and the University of Granada, and he
is the Chair of the Neuroscience Interest Group of the
International Society of Addiction Medicine.
Professor Verdejo-García has led numerous studies on
the cognitive and neural substrates of substance and
behavioral addictions, and new cognitive training and
remediation interventions for treating substance use dis-
orders. He is internationally recognized as an expert in this
field, as evinced by several international Editorial Board
positions including top-ranked addiction journals. He has
published more than 200 peer-reviewed articles, and his
work has attracted over 10,000 citations and has been
translated into clinical trials of neurocognitive interventions
and policy recommendations regarding application of
neuroscience principles for the prevention and treatment of
addictions.
xix
Foreword
Since the seminal paper of Dr. Leshnerdthen the director
of the National Institute on Drug Abusedin Science
in 1997, addiction is generally regarded to be a bio-
psychosocial disorder with strong genetic and neuro-
biological underpinnings and a chronic-intermittent course
with periods of recovery followed by relapse and often with
serious psychosocial deterioration. Based on animal studies
and human genetic and neuroimaging studies, Dr. Leshner
concluded that addiction is a brain disease and that addicted
people are patients who deserve (reimbursed) treatment.
According to the underlying biopsychosocial model,
addiction is the outcome of a preexisting hyperactive brain
reward system in combination with a deficient cognitive
control system in combination with neuroplastic changes
caused by continued drug use. Originally, the model was
predominantly presented in terms of dysfunctional brain
structures and neurotransmitter abnormalities with rela-
tively little attention to the cognitive representations of
these abnormalities. As a consequence, the link between the
neurobiological abnormalities and the behavioral mani-
festations of addictions was incomplete, and the search for
new treatments was mainly directed to the discovery of
new medications against relapse. Recent developments in
our knowledge about the neurocognitive aspects of the
development of addictive behaviors, the neurocognitive
consequences of chronic drug use, and the potential
treatments directed at improvement of preexisting and
drug-induced neurocognitive deficits have created new
hope for patients with an addiction.
This is the first book that provides a comprehensive
review of what we now know about cognition and addic-
tion. An impressive lineup of experts presents a broad and
in-depth overview of what is known about the cognitive
underpinnings of addiction, neurocognitive approaches to
treatment and future research perspectives.
The book starts with a well-balanced presentation of
what we know about preexisting (genetic and learned)
cognitive processes that are responsible for the change from
recreational drug use to goal-driven, drug seeking and finally
ending in chronic compulsive and habitual addictive
behaviors leading to physical and/or psychosocial decline
(Chapters 1e7). In addition to the well-known dual-process
model, the authors present extensions and/or integrated
variations of this model with new perspectives for treatment.
In the Chapters 14e16, similar reviews are presented for
gambling and gaming disorders.
In addition to their role as risk factors in the develop-
ment of addiction, cognitive impairments are often a
consequence of chronic, excessive drug use with negative
effects on the course of the disorder and on treatment
effectiveness. In the Chapters 8e13, reviews on the
consequences of drug use are presented for the different
substances of abuse, including alcohol, tobacco, cannabis,
cocaine, MDMA, and opioids. These chapters invariably
show not only that drug use may lead to cognitive
impairments but also that (sustained) abstinence will lead to
partial or complete recovery of cognitive functions and
probably to better long-term outcomes of treatment.
Treatment is the focus of the next part of the book
(Chapters 17e23). In a series of highly informative reviews,
the authors show that there are currently many more treat-
ment options than motivational interviewing and cognitive
behavioral treatment, including cognitive bias modification,
working memory training, inhibition control training,
goal management training, mindfulness-based relapse
prevention (MBRP), transcranial magnetic stimulation, and
the use of cognition-enhancing medications. With the
exception of approach bias modification and MBRP, these
new interventions need to be tested in large-phase III trials,
but most of them show great promise and will redirect
treatment from talking to training and from face-to-face
interventions to online treatments. In the last two chapters of
the book (Chapters 29 and 30), the authors provide an in-
tegrated review of both existing and new treatment options
and a theory-based proposal for optimal combinations of
cognitive interventions based on a thorough understanding
of the underlying cognitive models.
Chapters 24e28 are more contemplative in nature and
make the reader think about population neuroscience, the
use of cognitive information in combination with genetics,
the cognitive effects of reduced consumption versus
complete abstinence, and finally the (limited) impact of
scientific knowledge about cognition and addiction on
policy development.
This book is a remarkable set of reviews and position
papers presented as chapters edited by one of the best
xxi
xxii Foreword
scientists in the field of cognition and addiction. Thanks to
his broad and in-depth knowledge of the field and his
ability to recruit the best experts on such diverse topics;
this book is currently by far the best introduction to
cognition and addiction for neuroscience and psychology
students and researchers and for clinical psychologists,
psychiatrists, neurologists, and for all other people
interested in the topic. I therefore highly recommend this
book to everybody in the field.
Wim van den Brink, MD PhD
Em. Professor of Psychiatry and Addiction,
Amsterdam University Medical Centers,
Amsterdam, The Netherlands
Acknowledgments
The Editor (Antonio Verdejo-García) is funded by an
Australian Medical Research Future Fund, Next Generation
Clinical Researchers CDF2 Fellowship (MRFF 1141214)
and wish to acknowledge this support, trusting that the
book will contribute to the fellowship legacy by training a
new generation of addiction researchers. The Editor would
also like to acknowledge all the contributors for generously
sharing their unique knowledge and limited timedthey
make up an outstanding cast and are the ones who give true
value to this book. The Editor would also like to specially
acknowledge Professor Wim van den Brink, a trailblazer
addiction researcher and inspirational figure for many (back
then) young researchers in cognition and addiction and a
tireless supporter of early career scientists, for writing the
foreword of the book. Last not least, sincere acknowledg-
ments to the Elsevier editorial team including Joslyn
Chaiprasert-Paguio, who planted the first seed of this book,
and Tracy Tufaga, who has invaluably helped to make it
grow.
xxiii
Introduction
Cognition refers to mental processes and encompasses
“all forms of knowing and awareness, such as
conceiving, remembering, judging, imagining, and
problem solving” (APA Dictionary of Psychology).
Addiction is a mental health condition and, not surp-
risingly, is associated with cognitive biases and deficits.
The last 20 years have witnessed an unprecedented
expansion in the understanding of the cognitive
underpinnings of addiction vulnerability and chronicity.
This growth has been fueled by theoretical and techno-
logical advancement. Neurobehavioral models of addi-
ction have shed light on the cognitive mechanisms of
aberrant reward valuation, cognitive control, and
decision-making (Bickel et al., 2018; Everitt and Robbins,
2016; Goldstein and Volkow, 2002; Verdejo-Garcia and
Bechara, 2009), overcoming old views about addictive
behavior been “self-destructive” or “morally weak”
(discussed in Hyman, 2007, Am J Bioeth). The advent of
automated computerized testing, neuroimaging,
and other biomedical techniques such as gene
sequencing and manipulation, and novel intervention
approaches such as cognitive training and remediation,
neuroscience-informed psychotherapies and neuro-
modulation have fueled the knowledge gain and
revamped the landscape of cognition and addiction
research (Ekhtiari et al., 2019; Kwako et al., 2016;
Mackey et al., 2016). This book attempts to provide a
comprehensive view of this renewed landscape.
The book is structured in four main sections: (1)
Cognitive Principles, (2) Cognitive Risk Factors and
Consequences, (3) Cognitive Interventions, and (4)
New Vistas. Section (1) covers updated neurocognitive
theories of addiction and its evidence base. These
include views on addiction as a disorder that involves
an aberrant transition from impulsivity to compulsivity,
impaired response inhibition and salience attribution,
decision-making dysfunctions, social cognition and
interaction deficits, and personality comorbidities
underpinned by common alterations in executive
functions. Section (2) reviews the cognitive alterations
that underlie vulnerability to substance use and
gambling addictions, and the cognitive sequela asso-
ciated with the chronic use of different substances, such
as alcohol, cannabis, stimulants and opioids, and
gambling modalities. The cognitive profiles associated
with different drugs and addictive behaviors are dis-
cussed in the context of current topics and contro-
versies, such as the therapeutic effects of cannabinoids,
the aftermath of the synthetic opioid crisis, or the
advent of online gambling and gaming activities
(Curran et al., 2016; Karilla et al., 2018; Kardefelt-
Winther et al., 2017). Section (3) introduces novel
neuroscience-informed treatment approaches to
rescue cognitive deficits and improve clinical out-
comes for people with addictions. These approaches
include computerized cognitive training programs to
retrain salience-related biases and build response
inhibition and working memory capacity, cognitive
remediation therapies focused on executive functions,
mindfulness interventions targeting cognitive control
and monitoring, and pharmacological enhancement
and brain-stimulation techniques. Finally, Section (4)
provides unique new vistas on research approaches
that are pushing the boundaries of the cognition and
addiction field. These exciting new avenues include
population neuroscience, namely, the application of
cutting-edge neuroscience tools to population-based
cohorts, neuroepidemiology, i.e., the leverage of
epidemiology data to address neurocognitive ques-
tions, neuroethics, and longitudinal brain mapping. In
addition, it provides a pedagogic approach to the use
of new techniques for “big data” collection and
analysis, and the application of genetic and neuro-
imaging techniques to understand the lifespan of
addiction pathophysiology, from preterm vulnerability
to adult abstinence-based neuroplasticity and recovery.
The book has been conceived with an inclusive and
international perspective and includes contributors
from Europe, Africa, America, Australia, and the
Middle East, which provide a truly global viewpoint.
The contributors are outstanding researchers and
xxv
xxvi Introduction

clinicians, and the contents are geared towards a broad Biobehav. Rev. 104, 118e140. https://doi.org/10.1016/j.neubiorev.
audience including research students, researchers 2019.06.007. Epub 2019 Jul 2. Review. PubMed PMID: 31271802.
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habits to compulsions ten years on. Annu Rev Psychol 67, 23e50.
in learning and applying cognitive principles and
https://doi.org/10.1146/annurev-psych-122414-033457.
techniques in addiction research, prevention, assess-
Goldstein, R.Z., Volkow, N.D., 2002. Drug addiction and its underlying
ment, treatment, and recovery. We hope to succeed in neurobiological basis: neuroimaging evidence for the involvement of
our main goal, that readers share our enthusiasm about the frontal cortex. Am. J. Psychiatry 159 (10), 1642e1652.
this fascinating field. Hyman, S.E., 2007. The neurobiology of addiction: implications for
voluntary control of behavior. Am. J. Bioeth. 7 (1), 8e11.
Kardefelt-Winther, D., Heeren, A., Schimmenti, A., van Rooij, A.,
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Chapter 1
Cognition: the interface between nature
and nurture in addiction
Antonio Verdejo-Garcia
School of Psychological Sciences and Turner Institute for Brain and Mental Health, Monash University, Melbourne, VIC, Australia
Introduction
A key question in the field of addiction is whether some
people are hardwired to develop addictive disorders or if,
conversely, drugs and “addictive products” or related
contexts generate addictions. Historically, the answers to
this question have fluctuated as a function of prevailing
theories. Old moral views and personality models saw
inherent weaknesses in the individual (Eysenck, 1997;
Peele, 1987). Learning theories have focused on the ability
of drugs and “addictive products” (e.g., electronic gaming
machines) to generate aberrant learning, which is then
resistant to extinction relatively uniformly across
individuals (Robinson and Berridge, 2003, 2008). Social
theories have treated addiction as a manifestation of a
certain context and environment (e.g., the classic studies on
Vietnam War veterans) (Moore, 1993; Zinberg, 1984).
Nowadays, there is agreement that none of these models, in
isolation, can satisfactorily explain the nature and the
course of addiction, but at the same time, there is a lack of
comprehensive frameworks. Contemporary models have
embraced a biopsychosocial approach, but there is a bias
toward the bio-, at least in discovery science and thera-
peutic development, especially after the advent of neuro-
imaging tools and genetic manipulation techniques within
animal studies (Hall et al., 2015a). The current prevailing
view is that addiction is a “brain disorder,” characterized by
drug- or gambling-related neuroadaptations that ultimately
have an impact on psychological functioning (changes in
thinking, emotions, and behaviors) and social interaction
(Volkow et al., 2011; Volkow et al., 2016). Critics of this
view argue that it mistakenly reproduces a physical disease
model (inadequate for mental disorders or social
constructs), lacks integration of social and environmental
drivers, and fosters feelings of hopelessness and
Cognition and Addiction. https://doi.org/10.1016/B978-0-12-815298-0.00001-0
Copyright © 2020 Elsevier Inc. All rights reserved.
externalization among people with addiction (e.g., “I have a
disease, I can’t do anything about it”) (Hall et al., 2015b).
In this chapter, I will argue that a focus on cognitiond
encompassing thinking, emotion, and related behaviors,
as well as their neural underpinningsdcan provide a more
comprehensive and integrative understanding of the nature
and the course of addiction. Cognition sits at the interface
of biological, psychological, and social drivers of addictive
disorders, hinging on the interplay between nature and
nurture. Genetic and early environmental influences shape
the cognitive traits that make us vulnerable or resilient to
drug use/gambling and related social contexts (e.g., product
availability, peer pressure) (Belcher et al., 2014). At the
same time, drugs and gambling modify learning and
cognitive control processes and change the way we interact
with others and the environment (Everitt and Robbins,
2016; Goldstein and Volkow, 2011; Moeller and Goldstein,
2014). By focusing on cognition, we can overcome
the reductionism of the “disease model,” i.e., it’s not in
the brain, it’s at the interface between the brain and the
environment, and foster self-agency about recovery,
i.e., it’s not indelible, the same influences that originally
shaped cognition in a certain way can help restore or
compensate cognitive mechanisms to facilitate recovery
(Garavan and Weierstall, 2012). To articulate this vision,
I will first discuss the role of cognition in contemporary
addiction theories and outline a cognition-centered
integrative approach. Next, I will summarize cognitive
neuroscience evidence showing that individual variations in
core cognitive processes, particularly reward-related
processes and higher-order cognitive skills, plus
disorder-specific impacts on such processes, can explain
both addiction vulnerability and disordered states and
chronicity.
1
2 Cognition and Addiction
Cognition to bridge the gap between
neurobiological models and social
accounts of addiction
Contemporary theories of addiction generally posit neuro-
biological alterations in three systems: the incentive
salience (or reward) system, the stress system, and the
executive control system, which map into the striatum,
extended amygdala, and prefrontal cortex circuits, respec-
tively (Koob and Volkow, 2010). Incentive salience
alterations are responsible for reward sensitization
(increased motivation toward drugs/gambling resulting
from repeated administrationdi.e., instead of the expected
habituation) and reward prediction errors (i.e., expecting
more reward than what is actually received). Heightened
motivation toward drugs/gambling also occurs at the cost of
reduced motivation toward natural reinforcers (Goldstein
and Volkow, 2002, 2011). Alterations in the stress system
account for persistently elevated negative affect, which can
manifest as chronic stress and depression, as well as
predominance of negative reinforcement mechanisms in the
control of behavior. That is, negative affective states
become the norm, behaviors are mostly energized to try to
get rid of unpleasant feelings, and this behavior results in
short-term relief but long-term augmentation of the stress
response. Finally, executive alterations are responsible for
the tendency to focus on immediate responses and short-
term outcomes, neglecting goals and long-term conse-
quences. Different theories emphasize two or more of these
alterations and related brain systems. For example, “dual
models” focus on the imbalance between incentive salience
(ventral striatum) and executive control (dorsolateral
prefrontal cortex [DLPFC] and anterior cingulate cortex)
(McClure and Bickel, 2014). Stress models emphasize the
link between negative affect (hypothalamicepituitarye
adrenal axis, amygdala, hippocampus) and poor control
over stress-related responses (dorsal striatum, DLPFC),
which has been ascribed to impulsivity (e.g., negative
urgencydthe tendency to act impulsively under negative
affect) or compulsivity (e.g., repetitive behaviors that “fly
under the radar” of top-down executive supervision)
(Figee et al., 2016; Verdejo-García et al., 2007). Executive
control and decision-making models highlight the
misalignment between goal-related systems (ventromedial
prefrontal cortex) and motivational, emotional, and
contextual drivers (striatum, insula, amygdala/hippocam-
pus) (Bechara, 2005; Redish et al., 2008; Verdejo-García
and Bechara, 2009). Although the significance of these
models dwells in the way they characterize the drivers of
addictive behaviors, while acknowledging that these drivers
are shaped by and operate in social contexts, they often
come across as reductionist biological accounts of
behavior.
Translating the key notions of these models into a
cognitive framework can help to broaden their scope and
impact. Essentially, contemporary neurobiological theories
characterize the “backend” of addiction-related alterations.
The “frontline” is the complex harmful behavior and the
negative social consequences that policy makers and
preventionists try to counteract and clinicians have to face
(i.e., uncontrolled drug/gambling use, distress, deterioration
of health and quality of life, lack of social support, personal
and social burden). In between these two, there is a range of
cognitive alterations involving reward valuation and
learning, emotion processing and affect regulation, and
executive control and decision-making affecting personal
and social domains (e.g., valuation of individual rewards
such as salary and career and social rewards such as
friendships and relationships). And these alterations trace
back to specific traits that interact with environmental and
social factors before and during the emergence of addiction
and can potentially cooperate with contextual factors in the
path to addiction recovery (Celma-Merola et al., 2018).
As addictions take time to develop, we can chronologically
map the unfolding of cognitive drivers and their interaction
with environmental and social factors. Cognitive-affective
traits, such as reward sensitivity, negative affectivity, and
impulsivity/self-control, influence child and adolescent
learning and academic and social development. The inter-
action between these traits and environmental/social
influences (socioeconomic disadvantage, trauma, poor
parenting, academic failure, peer pressure or social isola-
tion) predicts the onset of addictive behaviors. Once
initiated, drug use and gambling contribute to exacerbate
preexisting traits, for example, they sensitize reward
learning and stress responses and deteriorate cognitive
control, fostering impulsive decisions and compulsive
behaviors. These changes contribute to worsen the
contextual milieu (i.e., loss of productivity, income, social
capital, and support) and foster a spiral of distress and
impoverishment of quality of life. Although this scenario
describes the “typical” developmental course of addictive
behaviors across adolescence and young adulthood, it can
also apply to late-onset addiction, in which interpersonal
and social factors (e.g., trauma, relationship problems,
unemployment) interact with cognitive characteristics
(e.g., emotion regulation and resilience against negative
affect, self-control, cognitive flexibility) as well as drug-
and gambling-related effects to generate protection against,
or escalation toward, addiction problems. Therefore,
cognitive traits predict the onset of addictive behaviors via
direct and indirect pathways (e.g., interaction with
academic and social factors and stressful life events). At the
same time, drug use and gambling deteriorate or exacerbate
cognitive traits and their underlying neural processes,
giving rise to abnormal cognitive states or cognitive
 Cognition: the interface between nature and nurture in addiction Chapter | 1
deficits, as well as contextual and social factors
(i.e., disordered states), leading to the vicious cycle of
addiction.
Evidence for the double role of
cognition in addiction vulnerability and
consequences
The view that cognition may be the key to unlock the
nature and the course of addiction stands on evidence from
longitudinal studies, endophenotype-based approaches, and
“neurotoxicity-controlled designs” comparing people with
addiction versus nonaddicted recreational users and people
with substance versus behavioral addictions. Longitudinal
designs enable researchers to identify cognitive traits as
well as other factors that predate the onset of addictive
behaviors and to track the changes that result from drug/
gambling use once initiated. It is worth noting that animal
studies can also successfully address this transition (from
trait characteristics to disorder-related states) but this
approach will be covered in Chapter 2, and thus here I will
only focus on human research. Endophenotype studies rely
on the assumption that cognition is an intermediate feature
between the biological drivers and the complex behavioral
manifestations of addictive disorders (Verdejo-García et al.,
2008). As such, the cognitive traits that predispose certain
people to addiction can be identified in their first-degree
relatives, and the cognitive differences between people
with addiction and their unaffected relatives reflect drug
use/gambling-related changes. Similarly, studies comparing
people with addiction and recreational users, or people with
substance versus behavioral addictions, can contribute to
disentangling addiction-related traits and addiction-
resulting deficits. In the following sections, I summarize
relevant evidence from each of these approaches.
Longitudinal studies
A key assumption of the cognitive framework articulated in
this chapter is that certain cognitive traits and skills predate
and influence onset of addictive behaviors. Before discus-
sing the evidence, it is important to note that although
“traits” and “skills” have been traditionally approached
from different disciplines, i.e., personality versus cognitive
sciences, respectively, now we know that they are mean-
ingfully intertwined and underpinned by common neural
circuits and processes. As an example, the construct of
“conscientiousness,” which has a long tradition in person-
ality science, is very similar to the concept of “cognitive
control” or “disinhibition” within modern cognitive
neuroscience (Nigg, 2017). In support of this view, these
two constructs have similar developmental trajectories
(peaking between 12 and 16 years during childhood and
3
adolescence) and overlapping brain underpinnings
involving lateral prefrontal cortex and anterior cingulate
regions (Vijayakumar et al., 2014a,b). Moreover, consci-
entiousness and cognitive control are strongly correlated
with intelligence quotient (IQ) and particularly fluid intel-
ligence, probably reflecting meaningful interactions
between trait characteristics and cognitive skills, as well as
between these two and some of the social-contextual
determinants of IQ (e.g., social disadvantage correlates
with low conscientiousness, poorer cognitive control and
low IQ) (Yücel et al., 2012). It could be argued that more
“affective” traits such as reward sensitivity or negative
emotionality do not fit in this pattern, but there are good
reasons to think they do. For example, the trait of reward
sensitivity overlaps with the ability to learn from reward
feedback, which is critical for cognitive and social devel-
opment as well as academic achievement (Telzer, 2016).
In this context, longitudinal evidence has established
that lower general cognitive skills, lower conscientiousness
(or higher disinhibition/impulsivity), and higher negative
affectivity predate and predict the onset of substance use/
gambling and the development of addictive disorders.
In population-based cohorts within the general population,
lower cognitive ability (IQ) measured in late adolescence
predicts the risk of subsequent substance addiction during
adult life (Latvala et al., 2016). Although the association
seems primarily due to genetic influences, these influences
are indirectly inferred from behavioral genetic analyses,
which can slightly overestimate genetic versus environ-
mental effects (Joseph, 2002; Kendler et al., 2016). Inter-
estingly, the most predictive aspects of IQ in relation to
addiction are the inductive and verbal domains (strongly
associated with cognitive control) versus the visuospatial
and technical domains. Within high-risk cohorts, which
target individuals at greater risk of developing addiction
problems by virtue of family history or personality, studies
have consistently found that high levels of impulsivity/
disinhibition (or low levels of conscientiousness and
cognitive control) measured in childhood predict the onset
of addictive behaviors in adolescence and the development
of addictive disorders (substance use disorders and
gambling disorder) during young adulthood (Acheson
et al., 2011; Lovallo et al., 2013; Slutske et al., 2012; Tarter
et al., 2004; Tarter et al., 2003). This association is direct
and significant after controlling for other environmental and
social factors (e.g., background, socioeconomic status,
parenting), although it is possible that some of these factors
conflate into impulsivity measures within the high-risk
samples. Recently, longitudinal studies have focused on
adolescence as a natural model of risk within the general
population and have incorporated multisite designs and
imaging measures as part of multimodal assessment
protocols including history (i.e., background characteris-
tics), personality, and cognitive/brain measures. One of
4 Cognition and Addiction
these studies, the IMAGEN consortium, found that a
combination of background characteristics, the personality
facets of conscientiousness and anxiety sensitivity, and
structural (GM:WM ratio; parenchymal volume) and
cognitive-evoked functional brain features (right precentral
gyrus activation during reward outcome and inhibition
failure and bilateral superior frontal gyrus during reward
outcome) predict future binge drinking (a proxy of prob-
lematic alcohol use and addictive behaviors) (Whelan et al.,
2014). Conversely, ventromedial prefrontal cortex activa-
tion during emotional reactivity and face recognition was a
better predictor of current binge drinking, probably
reflecting alcohol-related neuroadaptations.
Altogether, longitudinal results support the dynamic
model sketched in the previous sections, whereby cognitive
traits and difficulties associated with cognitive control/
disinhibition and negative affectivity contribute to addic-
tion vulnerability and are subsequently exacerbated by
addictive behaviors.
Endophenotype studies
In a series of studies including sibling pairs with the same
biological parents, one affected and one unaffected with
stimulant use disorders, Ersche and colleagues identified
cognitive and brain features associated with addiction
vulnerability (i.e., shared by affected and unaffected
siblings) and changes associated with stimulant use. With
regard to trait impulsivity, indicated by self-reports
reflecting different aspects of impulsiveness and novelty
seeking, stimulant users showed greater impulsivity than
both sibling and controls, but there were also sizable
differences between siblings and controls (Ersche et al.,
2010). Therefore, this approach shows that impulsivity is a
vulnerability factor for addiction, but crucially it is also
exacerbated by substance use. Interestingly, the main
differences between siblings and controls were in the
nonplanning aspect of impulsivity (theoretically associated
with the construct of conscientiousness) (Whiteside and
Lynam, 2001), whereas the main difference between
stimulant users and siblings was in the disinhibition aspect
of novelty seeking, which reflects behavioral dysregulation,
as manifested, for example, in uncontrolled drug use and/or
gambling. In a subsequent study that included trait
measures of impulsivity and compulsivity, emotional
sensitivity (negative affectivity and stress) and self-
evaluation (self-efficacy, locus of control, and social
comparison), and cognitive measures of executive control
and disinhibition, results showed that stimulant users,
siblings, and controls differed in most of these measures
(Ersche et al., 2012b). Both sibling pairs differed from
controls on impulsivityecompulsivity, negative affectivity,
and self-evaluation, suggesting that stimulant use exacer-
bates the traits that are already elevated in nonaffected
siblings. In the executive tests of working memory and
planning, stimulant users performed poorer than siblings
and controls, and siblings poorer than controls. Conversely,
inhibitory control measured with the Stop-Signal Task
(a motor impulsivity task) differed between the sibling pairs
and controls but not between stimulant users and their
siblings, suggesting that inhibitory control deficits are more
of a vulnerability for and less of a consequence of addic-
tion. Interestingly as well, there were no significant
differences between the groups on tests of memory or
attention, suggesting that only certain cognitive functions,
i.e., those related to cognitive control/executive functions,
play a crucial role in the nature and course of addiction.
Finally, structural neuroimaging measures revealed a set of
regions displaying overlapping abnormalities in both
stimulant users and their siblings, compared with healthy
controls: the putamen and the amygdala had both signifi-
cantly larger volumes, while the posterior insula, the left
postcentral gyrus, and the superior temporal gyrus had
lower volumes (Ersche et al., 2012a).
Altogether, endophenotype studies support the notion
that specific trait characteristics, including heightened
impulsivity and negative affectivity and related neural
systems, confer vulnerability to addiction and are subse-
quently exacerbated by drug use, leading to greater deficits
in executive functions and further behavioral dysregulation.
Neurotoxicity-controlled studies
This section summarizes the findings from two approaches:
(i) comparing dependent versus recreational cocaine users
and (ii) comparing substance users and gamblers. The first
approach offers insights into which aspects of cognition
deteriorate as a function of addiction progression (i.e., those
observable in dependent vs. recreational users and
controls). The second approach offers insights into which
aspects of cognition are more sensitive to substance-
induced neuroadaptations (i.e., those observable in
substance users vs. gamblers) and which aspects are related
to common vulnerability factors (overlapping between
substance users and gamblers and different from healthy
controls).
Dependent versus recreational users
In a series of studies by Quednow and colleagues, people
with cocaine addiction (meeting Diagnostic and Statistical
Manual of Mental Disorders [DSM] criteria for depen-
dence) and those with recreational cocaine use (but not
dependence) underwent trait and neuropsychological
assessments. Both groups used cocaine as their primary
drug (>40 g per month) and were currently abstinent, but
critically cocaine exposure was eight times higher in the
dependent versus the recreational group, as indicated by
 Cognition: the interface between nature and nurture in addiction Chapter | 1
hair toxicology analyses. With regard to trait and cognitive
aspects of impulsivity, findings showed significant differ-
ences between the two cocaine groups and controls in
general impulsiveness and novelty seeking. However, only
attentional-impulsive traits differed between dependent and
recreational usersdthey were higher in the dependent
group. In addition, there were no differences between the
groups on cognitive measures of disinhibition, including
attentional and motor impulsivity tasks (Rapid Visual
Processing or Stop-Signal Task) (Vonmoos et al., 2013b).
When examining executive functions, findings showed
significant differences between dependent users, recrea-
tional users, and controls in tests of working memory and
recall consistency (an index of strategic retrieval).
In addition, sustained attention was affected in recreational
users and correlated with cumulative cocaine exposure
(Vonmoos et al., 2013a). A subsequent study in this cohort
incorporated measures of decision-making, involving both
individual rewards and social rewards. Both dependent and
recreational cocaine users exhibited social decision-making
deficits (more self-serving behavior in social economic
exchange games). However, only dependent users showed
deficits in tasks involving individual-based rewards,
including the Iowa Gambling Task and Delay Discounting,
which also correlated with cocaine dose and duration
(Hulka et al., 2014).
Altogether, these studies suggest that impulsivity and
related cognitive constructs (sustained attention) represent
vulnerability factors or early signs of exposure to drug use,
whereas working memory and executive-memory retrieval
deficits are specific consequences of substance use.
Stimulant users versus gamblers
These studies compared the trait characteristics and the
cognitive performance of people with cocaine addiction
versus those with gambling disorder and minimal exposure
to substance use, which was restricted to alcohol abuse
(as per DSM-IV-TR) and smoking. In an initial study
examining trait impulsivity and executive functions,
findings showed that the negative urgency trait (acting
impulsively under negative affect) was higher in cocaine
users versus gamblers and controls and higher in gamblers
than controls. Conversely, positive urgency (acting impul-
sively under negative affect) was elevated in cocaine users
and gamblers versus controls (showing no differences
between each other) (Albein-Urios et al., 2012). The anal-
ysis of executive function tests showed that cocaine users
had poorer working memory than both gamblers and
controls, whereas response inhibition performance
(measured with an attentional inhibition task, the Stroop
Test) was similar among cocaine users and gamblers and in
both cases poorer than in controls. A subsequent study
examined the same cohort using the brain and behavioral
5
measures of cognitive flexibility (reversal learning perfor-
mance and related brain activation) (Verdejo-Garcia et al.,
2015). The perseveration error rate (an index of cognitive
inflexibility) was higher in cocaine users versus gamblers
and controls. In addition, cocaine users showed less
DLPFC activation during reversal shifting (i.e., the “flexi-
bility” trials) versus gamblers and controls, whereas both
cocaine users and gamblers showed reduced ventrolateral
prefrontal cortex (VLPFC) activation compared with
controls and no differences between each other. The
DLPFC is strongly and generally implicated in executive
control and seems to be specifically affected by cocaine
use, whereas the VLPFC is more specifically implicated in
goal-related cognitive control and seems to be similarly
associated with cocaine and gambling use.
Altogether, these studies suggest that positive urgency
and reduced response inhibition represent vulnerability
factors for substance use and behavioral addictive disor-
ders, whereas working memory and cognitive flexibility
deficits are specific consequences of substance use.
Cognition at the interface between
nature and nurture
Here, I started by proposing that cognition sits at the
interface between the vulnerability for and the conse-
quences of addiction and that it is pivotal to understand the
interplay between individual-based factors (genetics,
neuroadaptations) and environmental and social drivers.
The evidence reviewed suggests that an array of
cognitive traits and skills, which encompasses “personal-
ity” concepts of conscientiousness and negative affectivity
(as manifested in emotional sensitivity or negative urgency)
and “cognitive” constructs associated with fluid intelli-
gence, attention, (dis)inhibition, and social decision-
making, are part of the vulnerability to substance use and
behavioral addictive disorders, whereas traits associated
with behavioral dysregulation and cognitive deficits in
working memory, cognitive flexibility, and reward-based
decision-making are associated with the consequences of
substance and behavioral addictions. Of note, there is an
important overlap and continuity between premorbid traits
and “disordered states,” given conceptual similarities and
shared variance between, e.g., fluid intelligence, conscien-
tiousness, and executive functions.
The relevance of social cognition processes in the
vulnerability to addiction (revealed by endophenotype and
neurotoxicity-controlled studies) also illustrates the inter-
active nature of cognitionedrugs/addictive productse
environment relationships, as faulty social decision-making
processes can facilitate deviant social behavior (reduced
social integration or heightened sensitivity to peer pressure)
and drug/gambling use, which can ultimately exacerbate
6 Cognition and Addiction
and broaden social-cognitive deficits, fostering a vicious
cycle of social impoverishment.
Cognition is central to addiction development and
maintenance. Higher-order cognitive traits and processes
such as conscientiousness and cognitive control over salient
stimuli (attention) and emotions (negative affectivity) as
well as social-cognitive characteristics determine vulnera-
bility for addictive disorders. At the same time, substance
use and behavioral addictions are associated with cognitive
deficits in working memory, mental flexibility, and reward-
based decision-making, which are essential for goal
achievement and successful social interactions. These
cognitive alterations can then contribute to explaining the
core manifestations of addiction (e.g., the persistence of
behavior despite negative consequences, recurrent cravings,
relapses) and compromise treatment and recovery goals.
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Chapter 2
From impulses to compulsions
Kavya Raj1 and Antonio Verdejo-Garcia2
1
Brain, Mind and Society Research Hub, Monash University, Melbourne, VIC, Australia; 2School of Psychological Sciences and Turner Institute for
Brain and Mental Health, Monash University, Melbourne, VIC, Australia
Introduction
Addiction can be conceptualized as a loss of control over
drug-seeking and -taking behavior, whereby drug use that
was initially voluntary and recreational progresses to a
habit, and ultimately a compulsion, continuing to persist
despite harmful consequences (Belin et al., 2013; Everitt
and Robbins, 2005, 2013, 2016). It is hypothesized that this
behavioral transition from impulsive choices to compulsive
drug seeking and taking is underpinned by a shift in the
neural loci of control from the ventral to the dorsal striatum
(Belin and Everitt, 2008; Everitt and Robbins, 2013, 2016),
as well as a progression from prefrontal cortical to
subcortical striatal control (Chen et al., 2013; Everitt and
Robbins, 2016; Murray et al., 2012; Renteria et al., 2018).
This chapter summarizes the animal and human evidence
that sustains this notion, starting with preclinical studies,
continuing with human neuroimaging and cognitive
studies, and concluding with ideas for future directions.
Animal models of drug-seeking habits
and compulsions
A key approach to understanding the transition from
voluntary to compulsive drug use is through the lens of
Pavlovian and instrumental learning (Robbins and Everitt;
Everitt and Robbins, 2013). According to this perspective,
initial drug use is goal-directed and controlled by action-
outcome (A-O) mechanisms. In this context, drug-related
actions are sensitive to changes in outcome value, and
thus drug seeking can stop if drug value decreases or is
outweighed by alternative reinforcers (Everitt and Robbins,
2005). However, as drug use escalates, a parallel instru-
mental learning mechanism comes to dominate responding,
and behavior shifts to a stimuluseresponse (S-R) habit
process that is insensitive to outcome devaluation, i.e.,
precludes stopping or changing behavior, even when the
Cognition and Addiction. https://doi.org/10.1016/B978-0-12-815298-0.00002-2
Copyright © 2020 Elsevier Inc. All rights reserved.
outcomes of such behaviors are negative (Zapata et al.,
2010). Environmental stimuli associated with the effects of
drug self-administration gain incentive salience via
Pavlovian conditioning, and drug-seeking responses are
automatically elicited by conditioned S-R loops (Everitt
and Robbins, 2005). Drug-seeking and -taking behavior
controlled by this S-R process is severed from the value of
the drug and can operate without full engagement of
cognitive control processes (Belin et al., 2013). Whether
drug use is controlled by A-O or S-R mechanisms, at a
behavioral level, can be tested through outcome devalua-
tion procedures to observe whether instrumental respond-
ing for drug rewards changes as the outcome value changes
(Dickinson et al., 2002).
The shift from A-O to S-R mechanisms mediating drug
use is documented by a consistent body of animal research.
In a sophisticated series of experiments, Olmstead et al.
(2001) utilized a heterogenous chained schedule of intra-
venous cocaine self-administration in which rats performed
an initial drug-seeking response, which in turn provided
access to a secondary drug-taking response that resulted in
delivery of cocaine. After briefly establishing cocaine self-
administration, drug-seeking responses were shown to be
sensitive to devaluation when the taking link of the chained
schedule was extinguished, indicating that at an initial stage
of cocaine seeking, behavior is goal-directed and influenced
by the value of the response outcome. To replicate and
extend this finding, Zapata et al. (2001) utilized a modified
chained schedule of intravenous cocaine self-administration
and demonstrated that, following a moderate number of
training sessions, initial cocaine seeking is goal directed
and sensitive to devaluation. However, as sessions
increased and the cocaine-seeking experience was
extended, 43% of the sample continued to respond after the
outcome had been devalued, indicating that drug-seeking
behavior had become habitual for this subgroup and was
operating through an S-R mechanism. Similarly, while
9
10 Cognition and Addiction
instrumental responding for alcohol at early stages of
training is goal-directed, after 8 week of training, behav-
ioral control over alcohol seeking shifts to S-R habit
mechanisms and is no longer sensitive to devaluation
(Corbit et al., 2012). These findings illustrate how escala-
tion of drug use results in resistance of drug seeking to
outcome devaluation, and thus habitual S-R behaviors.
While habitual drug-seeking and -taking behavior alone
cannot provide a comprehensive explanation for addiction,
it provides the foundation for compulsive drug use (Everitt
and Robbins, 2016). Perseveration of habitual drug-seeking
behavior despite drastically negative outcomes, such as
deterioration of health and family bonds or loss of social
support and employment, is a core aspect of addiction
(Ersche et al., 2011). Aversive conditioning studies in rats
show that, after sufficient training and exposure, respond-
ing for oral cocaine (Miles et al., 2003) and alcohol
(Dickinson et al., 2002) perseveres even after devaluation
through nausea-inducing lithium chloride injections
(Nachman, 1963). Recent evidence suggests that as few as
16 training sessions are sufficient to render alcohol-seeking
behavior unresponsive to devaluation through aversive
conditioning (López et al., 2016). Drug reinforcers are
significantly more resistant to aversive conditioning than
natural foodebased reinforcers, for which responding is
more readily reverted to an A-O process, perhaps due to
evolutionary reasons (Dickinson et al., 2002; Miles et al.,
2003). This indicates that drug reinforcers induce an S-R
habit process far more rapidly than natural rewards.
Moreover, drug-induced difficulty to shift between S-R and
A-O processes suggests that a dominant habit system may
become “compulsive” and trigger automatic drug-seeking
behaviors under aversive conditions.
Neural circuits: transitioning from the
ventral to dorsal striatum
Converging evidence from animal research shows that the
transition from voluntary to habitual and eventually
compulsive use is neurally underpinned by a progression
from the ventral to the dorsal striatum, via dopaminergic
circuits (Belin and Everitt, 2008; Everitt and Robbins,
2005; Vanderschuren et al., 2005; Vanderschuren and
Everitt, 2005). This transition has been neatly revealed in
animal models of stimulant addiction. Early acquisition of
cocaine seeking depends on the nucleus accumbens core, a
region of the ventral striatum; lesions to this area disrupt
establishment of drug-seeking behavior (Ito et al., 2004).
Yet, as cocaine exposure escalates and becomes chronic,
drug-related neuroadaptationsdsuch as changes in meta-
bolic activity and density of dopamine transporter binding
sitesdincreasingly extend from the ventral striatum to
encompass dorsal striatal regions, the caudate and putamen
(Letchworth et al., 2001; Porrino et al., 2004). In rats with
well-established habitual cocaine-seeking behavior,
presentation of drug-related cues during cocaine seeking
results in marked increases of extracellular dopamine in the
dorsal striatum but not in the nucleus accumbens core or
shell (Ito et al., 2002). Moreover, dopamine receptor
antagonist infusion into this region of the dorsal striatum in
which elevated extracellular dopamine is detected signifi-
cantly reduces S-R driven, cocaine-seeking behavior
(Belin and Everitt, 2008; Vanderschuren et al., 2005). The
same infusion in the nucleus accumbens, however,
produces no effect on habitual cocaine seeking (Vander-
schuren et al., 2005), indicating that once behavior has
become S-R dominant, ventral striatal regions that are
entwined with A-O mechanisms lose influence over actions
that have become compulsive.
In addition to the ventral striatum progressively losing
control over drug-seeking behavior, the transition from
voluntary to compulsive drug use is further underpinned by
a transition within competing regions of the dorsal striatum:
from the posterior dorsomedial striatum (pDMS, early
acquisition) to the anterior dorsolateral striatum (aDLS,
habitual drug seeking) (Balleine et al., 2009; Murray et al.,
2012; Yin et al., 2004). Electrophysiological evidence from
rodents performing motivational tasks shows that early
acquisition correlates with DMS activity, but as training
extends and behavior becomes S-R dominant, DLS activity
increases (Thorn et al., 2010). At early stages of cocaine
self-administration, pharmacologically disabling the pDMS
by infusing that region with a D2 agonist infusion reduces
initial cocaine seeking (Murray et al., 2012). At the same
time point, deactivating the aDLS with the same D2 agonist
infusion has no effect on cocaine seeking, indicating that
early A-Oedriven, drug seeking is dependent on the DMS
and not the DLS. However, once self-administration is
well-established and S-R driven, cocaine-seeking behavior
can only be reduced by disabling the aDLS, whereas
disabling the pDMS had no effect on behavior (Murray
et al., 2012). A similar study utilizing microinjections of
lidocaine to deactivate striatal regions has shown that
disabling the DLS in cocaine-seeking rats can successfully
renew A-O control over compulsive cocaine-seeking
behavior (Zapata et al., 2010), signifying that, within the
dorsal striatum, the DMS relinquishes control to the DLS as
drug use becomes S-R driven. Similar findings are reported
for alcohol seeking (Corbit et al., 2012). Deactivating the
DMS at early stages of alcohol exposure shifts control to
the habit system, preventing behavior from being sensitive
to devaluation. However, after prolonged alcohol exposure,
deactivation of the DLS (yet not DMS) is needed to reen-
gage the goal-directed system. Moreover, this rich body of
research suggests that control over actions occurs through
competing goal-directed (DMS) and habit (DLS) systems,

and that while typically the DMS and DLS are simulta-
neously able to control the same behavior (Renteria et al.,
2018; Yin et al., 2006), this competition may be repeatedly
dominated by the DLS in substance use disorders,
ultimately resulting in compulsive drug use.
It is important to note that while control of behavior
may devolve to the DLS, ventral regions of the striatum
may continue to influence and interact with the dorsal
striatum. Belin and Everitt (2008) showed that combining a
unilateral lesion of the nucleus accumbens core with
contralateral dorsolateral striatum dopamine receptor
blockade reduces habitual cocaine intake, yet leaving newly
learned instrumental-seeking responses unaffected (Belin
and Everitt, 2008; Everitt and Robbins, 2016). Therefore,
notwithstanding the progressive transition from ventral to
dorsal striatal regions, ongoing interactions between the
nucleus accumbens core and DLS will have a critical role in
the formation and persistence of compulsive drug-seeking
behavior.
Devolving from prefrontal to striatal
control
Along with the progressive strengthening of DLS-driven
S-R habit processes, compulsive drug use is concurrently
mediated by weakened prefrontal control over striatal
regions (Koob and Volkow, 2010; Renteria et al., 2018).
Habitual behavior that occurs in the face of aversive con-
ditions would typically promote the transition back to A-O
processes and encourage ventral striatal regions to regain
control of behavior (Everitt and Robbins, 2016; Murray
et al., 2012); however, in substance use disorders, drug-
seeking behavior perseveres despite harmful outcomes
(Ersche et al., 2011). Dorsomedial and ventral striatal
regions that are integral to the functioning of the
goal-directed system receive prefrontal cortical projections,
and prefrontal cortex (PFC) hypofunction has been reported
across substance use disorders (Goldstein and Volkow,
2011). Thus, a contributing factor to the development and
maintenance of compulsive drug seeking may be hypo-
function of prefrontal regions and weakened cortical
projections to the striatum, which enables the DLS habit
system to remain dominant in controlling behavior
(Limpens et al., 2014).
Animal studies indicate that hypofunction of the
prelimbic cortexdwhich is homologous to the dorsolateral
prefrontal cortex (DLPFC) in humans (Bizon et al., 2012;
Koob and Volkow, 2016)dmay be tightly linked to
compulsive drug seeking (Chen et al., 2013; Bishop et al.,
2010; Limpens et al., 2014). In fact, lesions to the prelimbic
area enable the formation of inflexible S-R habits (Killcross
and Coutureau, 2003). A seminal study by Chen et al.
(2013) demonstrated that, in rats that compulsively seek
From impulses to compulsions Chapter | 2 11
cocaine despite electric foot shocks, extended cocaine
self-administration induced substantial hypoactivity in the
prelimbic cortex. Furthermore, in vivo optogenetic stimu-
lation of the prelimbic cortex significantly diminished
cocaine-seeking responses. In contrast, in vivo optogenetic
inhibition of the prelimbic cortex during cocaine
self-administration significantly increased cocaine-seeking
responses. More recent work by Limpens et al. (2014)
provides comparable findings and directly implicates the
prelimbic cortex in loss of executive control. Inactivation of
the prelimbic cortex significantly reduces a previously
conditioned suppression of cocaine seeking in rats, thereby
enabling the expression of compulsive drug-seeking
behavior. Hypofunction of the prelimbic cortex has also
been reported in opiate reward learning, wherein down-
regulation of prefrontal-excitatory N-methyl D-aspartate
receptors substantially increases sensitivity to the
rewarding effects of opiate administration (Bishop et al.,
2010). Together, these results not only indicate that
extended drug use induces marked neuroplastic changes in
prefrontal excitability but also that these changes are
critically involved in the expression of compulsive drug-
seeking behavior. Moreover, when considered alongside
previous animal research (Belin and Everitt, 2008; Zapata
et al., 2010), these findings support the hypothesis that
compulsive drug-seeking behavior may be driven by
a combination of DLS hyperactivation and prelimbic/
frontal hypoactivation, whereby weakened prefrontal
activity enables the striatum and habit system to maintain
control.
In addition to the prelimbic cortex, hypoactivation of
the orbitofrontal cortex (OFC) (key region for decision-
making in humans) has also been implicated in compul-
sive drug-seeking behavior (Renteria et al., 2018). Habitual
ethanol use in mice induces marked reductions in OFC
excitability (Renteria et al., 2018). The OFC directly
projects onto the DMS and is critically involved in excit-
atory circuits of the goal-directed system (Renteria et al.,
2018). Ethanol-induced suppression of OFC excitability
reduces glutamatergic transmission from the OFC to the
DMS via the direct output pathway and thus disrupts
goal-directed control over ethanol-seeking behavior
(Renteria et al., 2018). Importantly, stimulating the OFC to
increase excitatory activity in the OFC-striatal circuit
notably reinstates goal-directed control over previous S-R
ethanol-seeking behavior (Renteria et al., 2018). Yet
again, these findings indicate that habit-driven drug seeking
may stem from drug-induced OFC hypoactivation and
subsequent disruption of communication to striatal regions
critical for goal-directed control. Collectively, animal
research across models of various substance use disorders
indicates that compulsive drug-seeking behavior may arise
from a complex interaction between an intrastriatal shift
12 Cognition and Addiction
toward dorsolateral control and PFC hypoactivation, which
together enable rigid S-R habit processes to continue con-
trolling and perpetuating drug-seeking behavior under
harmful or aversive conditions.
Translating animal models to
understand compulsivity in people with
substance use disorders
Advancing from animal research, human studies also
indicate that compulsive drug use may be underpinned by
an over reliance on S-R mechanisms as well as prefrontal-
striatal adaptations (Ersche et al., 2011; Sjoerds et al., 2013;
Vollstädt-Klein et al., 2010). In this section, we focus on
cue-reactivity studies, in which drug-related cues are used
to provoke a conditioned craving response analogous to
habitual S-R behaviors (Koob and Volkow, 2010; Pickens
et al., 2011; Sinha and Li, 2007; Tricomi et al., 2009; Yoder
et al., 2009). Craving (a compelling desire to use the drug)
is a paramount clinical phenomenon and a proxy of
compulsive drug use in clinical studies (Skinner and Aubin,
2010; Tiffany et al., 2012). The cue-reactivity procedure
enables researchers to observe behavioral and neural
responses to drug-related cues, providing an indirect
measure of the severity of compulsive and automatic
responding in drug users (Carter and Tiffany, 1999;
Tricomi et al., 2009).
A consistent finding that emerges in cue-reactivity
studies across various substance use populations is the
importance of the dorsal striatum (caudate and putamen in
humans) in the transition from recreational to compulsive
use (Ersche et al., 2011, 2012a,b; Sjoerds et al., 2013;
Volkow et al., 2006; Wong et al., 2006; Zhou et al., 2018).
Early functional magnetic resonance imaging (MRI) and
positron emission tomography studies in cocaine users
established that cue-induced craving is associated with
increased metabolic activity, dopamine release, and dopa-
mine receptor occupancy in the dorsal striatum (Garavan
et al., 2000; Volkow et al., 2006; Wong et al., 2006).
Interestingly, the caudate (which is the human homologue
of the DMS in rodents; Balleine and O’Doherty, 2009)
response to sexually explicit stimuli is blunted in cocaine
users, suggesting that S-R tendencies are sensitized to drug
cues and relatively insensitive to natural reinforcers
(Garavan et al., 2000). Furthermore, increases in dopamine
receptor occupancy (Wong et al., 2006) and dopamine
release (Volkow et al., 2006) in the dorsal striatum are
proportionate to increases in cue-induced cocaine cravings
and also corresponded with addiction severity (Volkow
et al., 2006). In addition to functional differences, structural
MRI studies indicate that, when compared with their
noncocaine using siblings, cocaine-dependent individuals
have enlarged putamen volumes (Ersche et al., 2011, 2013),
which may suggest that greater dorsal striatal volume
increases risk for drug-related S-R conditioning and
substance use disorders (Everitt and Robbins, 2016).
Together, these findings suggest that dorsal striatal regions
(the putamen and caudate) are crucial to S-R driven
habitual craving responses in cocaine users, and that
dopamine dysfunction within these regions may play a
fundamental role in the severity of drug use.
Similar findings have been reported in alcohol-
dependent individuals (Sjoerds et al., 2013, 2014;
Vollstädt-Klein et al., 2010). Alcohol-related cues provoke
greater cue-induced activation in the left dorsal striatum in
heavy drinkers (Schulte et al., 2012; Vollstädt-Klein et al.,
2010). In addition, Vollstädt-Klein et al. (2010) found that
while heavy drinkers show more cue-evoked activation in
the dorsal striatum, light drinkers show a stronger response
in the ventral striatum. Moreover, they showed a significant
positive relationship between activation of the dorsal
striatum and scores on an obsessive-compulsive scale
(a proxy of compulsivity), whereas ventral striatal activa-
tion had a negative relationship with the same scale. This
study provides persuasive support for the notion of a
ventral to dorsal striatal control shift as alcohol use
becomes more severe and compulsive (Vollstädt-Klein
et al., 2010). More recent work by Sjoerds et al. (2013,
2014) has shown that, during an instrumental learning task
designed to explore potential imbalances between goal-
directed and habit learning processes, alcohol-dependent
individuals demonstrate a significant overreliance on S-R
habit learning, resulting in poor task performance
outcomes. Additionally, poor task performance coincides
with decreased activation of brain regions implicated in
goal-directed processes and increased activation in habit
learning brain regions, namely the posterior putamen
(analogous to the DLS in rodents). These results provide
considerable evidence to indicate an overactive and
inflexible habit system in alcohol-dependent individuals,
which appears to heavily depend on dorsal striatal regions
(Sjoerds et al., 2013). Furthermore, duration of alcohol
dependence was strongly associated with greater
cue-induced activation of the posterior putamen (Sjoerds
et al., 2014), further supporting the hypothesized ventral to
dorsal striatal shift as behavior advances toward addiction.
As the putamen is analogous to the DLS in rodents and the
caudate analogous to the DMS, this is a crucial detail for
the S-R habit hypothesis first proposed by Everitt and
Robbins (2005), which would predict greater putamen
adaptations as seen in rodent studies (Everitt and Robbins,
2016).
Changes in neural activation and adaptations in the
dorsal striatum are also observed in nicotine- (McClernon
et al., 2009) and cannabis-use disorder groups (Zhou et al.,
2018, 2019). Following a 24-h period of abstinence in adult
tobacco smokers, smoking cues elicited greater activation

in the dorsal striatum, specifically the putamen, relative to
neutral cues (McClernon et al., 2009). Participants with
cannabis dependence, compared with drug-naïve controls,
show an aberrant pattern of functional connectivity
involving less efficient communication between both
ventral and dorsal striatum and the PFC (Zhou et al., 2018).
More specifically, when comparing dependent versus
nondependent cannabis users exposed to a cue-reactivity
paradigm, dependent users alone demonstrated heightened
dorsal striatal activation during cue exposure (Zhou et al.,
2019).
Cumulatively, the results of human imaging cue-
reactivity studies support the consensus within animal
literature and suggest that dorsostriatal adaptations are
involved in compulsive drug use. In addition to evidence of
dorsostriatal changes, human studies also implicate hypo-
activation in multiple prefrontal regions across substance
use disorders (Goldstein and Volkow, 2011; Zilverstand
et al., 2018; see Chapter 3 in this book), much the same as
animal research. Individuals with alcohol use disorder
exhibit decreased engagement of the ventromedial PFC
(encompassing the OFC), which directly projects to the
ventral striatum, indicating OFC-striatal dysfunction
(Sjoerds et al., 2013). Similarly, individuals with alcohol
use disorder who relapse into compulsive use show hypo-
activation of the medial PFC during a goal-directed
decision-making task (Sebold et al., 2017), again suggest-
ing disrupted prefrontal control of behavior. Structural
imaging research by Ersche et al. (2013) demonstrates
significant reductions in OFC gray matter volume in
compulsive cocaine users, while recreational cocaine users
exhibit increased OFC volume. The increase in gray matter
volume for recreational users may reflect a protective factor
or potential resilience against progressing to compulsive
drug use (Ersche et al., 2013). Lastly, more recent
preliminary research aiming to directly translate animal
studies on hypoactivation of the prelimbic cortex (which is
the homolog of the human DLPFC) and optogenetic
stimulation has utilized repetitive transcranial magnetic
stimulant (rTMS) to electrically stimulate the DLPFC in
human cocaine users (Terraneo et al., 2016). rTMS of the
DLPFC significantly improved symptomology in
individuals with cocaine use disorder, as well as substan-
tially reducing craving for cocaine, signifying that as with
in vivo optogenetic stimulation of the prelimbic cortex in
animals reducing cocaine-seeking responses, electrical
stimulation of the human homolog has similar potential to
reduce drug-seeking behaviors (Terraneo et al., 2016).
For a more detailed discussion on brain stimulation
findings, see Chapter 22 of this book.
Altogether, findings from structural MRI, functional
imaging using tasks of cue-reactivity (dorsal striatal
hyperactivity) and decision-making (PFC hyporeactivity),
and emerging brain stimulation studies indicate that PFC
From impulses to compulsions Chapter | 2 13
hypoactivation may strongly contribute to the perpetuation
of compulsive drug-seeking behavior, wherein multiple
prefrontal regions are critically involved in enabling dor-
sostriatal S-R control of behavior.
Recommendations for future research
Animal experiments and cross-sectional human neuro-
imaging studies strongly support the role of dorsal striatal
control and weakened prefrontal regulation in compulsive
drug use. However, human studies have not yet fully
demonstrated the proposed dynamic shift between im-
pulses and compulsions or ventral to dorsal striatal control
that putatively occurs in each individual over time. We
propose two ways to trace this dynamic shift in the future.
One is through longitudinal studies. Assessing PFC-
striatal function and related phenotypes (cue-conditioned
craving, impulsivity, and compulsivity) among children
and adolescents before exposure to drugs and then
throughout adolescence and young/mid adulthood would
compellingly tell us if neural and cognitive transitions
similar to those observed in animals occur over the course
of human addiction. The advent of new ambitious and
exciting longitudinal research initiatives, such as the
Adolescent Brain Cognitive Development (ABCD) study
(https://abcdstudy.org/), has created a unique opportunity
to pursue this otherwise incredibly complex challenge.
The ABCD study will track the neurobiological and
behavioral development of >11,000 children and includes
detailed measures of cognition, brain function, and drug
use, providing a unique opportunity to address longitudi-
nal research questions. The study also has a remarkable
open data sharing policy, opening endless possibilities for
early career researchers. Another potential approach is
using rapidly evolving epigenetic tools. Discovering
epigenetic markers of ventral and dorsal striatal nuclei
gene expression and conducting intraindividual analyses
of changes in these markers over the course of substance
use and addiction, paralleled by detailed phenotyping,
would be another persuasive (although currently futuris-
tic) approach.
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Chapter 3
Dual models of drug addiction: the
impaired response inhibition and
salience attribution model
Anna Zilverstand1 and Rita Z. Goldstein2
1
Department of Psychiatry, University of Minnesota, Minneapolis, MN, United States; 2Departments of Psychiatry and Neuroscience, Icahn School of
Medicine at Mount Sinai, New York, NY, United States
Dual models of addiction
Addiction is a chronically relapsing disorder, characterized
by continued drug seeking despite reduced pleasure from
drug-taking and substantial negative consequences to the
individual and their kin. Neurobiological models of drug
addiction seek to explain this perplexing phenomenon by
understanding the changes in the brain driving this
behavior. Early neurobiological models focused on the role
of the reward system (also named “reinforcement,”
“approach,” “drive,” “motivational,” or “dopamine” sys-
tem), proposing that it was the repeated activation of the
positive reinforcement system that fueled repeated drug
taking (Wise and Bozarth, 1987). This theory was later
refined as the “incentive-sensitization theory,” which pro-
posed that the attribution of incentive salience is the un-
derlying function of the dopaminergic system, and that the
increased attribution of salience to drugs or drug cues is
associated with a “sensitization” or upregulation of this
system in drug addiction (Robinson and Berridge, 1993).
However, while these early models explained how drug
taking would propel the urge to seek drugs, they could not
explain the inability of addicted individuals to inhibit this
urge (Jentsch and Taylor, 1999). Therefore, later dual
models of addiction proposed an interaction between a
“drive” system (e.g., the reward system) and a “control”
system located in the prefrontal cortex, which would need
to be deployed to inhibit a sensitized reward system, but
shows impairments with chronic drug use (Jentsch and
Taylor, 1999). A contemporary updated dual model, pri-
marily based on evidence from human neuroimaging
studies, is the impaired Response Inhibition and Salience
Attribution (iRISA) model (Goldstein and Volkow, 2002,
2011; Zilverstand et al., 2018). The iRISA model proposes
Cognition and Addiction. https://doi.org/10.1016/B978-0-12-815298-0.00003-4
Copyright © 2020 Elsevier Inc. All rights reserved.
that the impairments of two neuropsychological
functionsdimpaired response inhibition and salience
attributiondand their underlying neural substrates
contribute to the clinical symptomatology of addiction
encompassing craving, intoxication, bingeing, and with-
drawal across a broad range of substance addictions,
including nicotine, alcohol, and illicit drug addictions
(Goldstein and Volkow, 2002, 2011; Zilverstand et al.,
2018). This model proposed for the first time that broad
higher-order cognitive functions involved in the “ability to
track, update, and modulate the salience of a reinforcer as a
function of context and expectation” and the “ability to
control and inhibit prepotent responses,” and their under-
lying neural networks, were impaired in human drug
addiction (Goldstein and Volkow, 2002). Indeed, recent
evidence suggests that impairments in iRISA in human
drug addiction are linked to the altered function of six
large-scale brain networks: the limbic-orbitofrontal reward
network, the fronto-insular-parietal salience network, the
prefrontal executive network, the fronto-parietal self-
directed network, the subcortical habit, and memory net-
works (Fig. 3.1). The conclusions made and the evidence
reviewed in this chapter are, unless stated otherwise, a
summary of the evidence discussed in a systematic review
of 105 task-related neuroimaging studies published from
2010 until 2018, which compared individuals with alcohol,
cannabis, heroin, stimulant, and other addictions to healthy
controls (Zilverstand et al., 2018). With very rare excep-
tions, findings were consistent across different drug-
addicted populations and are hence discussed under the
assumption that the iRISA model provides a common
model of addiction, independent of the primary drug of
choice.
17
18 Cognition and Addiction

FIGURE 3.1 Evidence from more than 100 neuroimaging studies in drug-addicted individuals supports dual models of addiction, such as the impaired
response inhibition and salience attribution (iRISA) model. Findings demonstrate that abnormal levels in the reward and salience networks can be linked
to a shift in incentive salience, with decreased incentive salience of nondrug-related stimuli and increased salience of drug-related cues, whereas changed
function of the salience and executive networks underlies impaired response inhibition. Additionally, neuroimaging data suggest that altered function of
the habit, memory, and self-directed networks underlie altered learning processes linked to both impaired response inhibition and salience attribution.
Adapted from Zilverstand, A., Huang, A.S., Alia-Klein, N., Goldstein, R.Z., 2018. Neuroimaging impaired response inhibition and salience attribution in
human drug addiction. A systematic review. Neuron 98, 886e903.

Neuroimaging evidence for dual models
The reward network consists of the ventral striatum, sub-
genual/rostral cingulate, and orbitofrontal and anterior
prefrontal cortex, which together support the appraisal of
incentive value by estimating subjective value based on
expected reward outcomes. This network has been termed
the “reward network,” as these brain regions show a
consistently strong response during rewarding events (in
contrast to the “salience network,” which reacts robustly to
both pleasant and unpleasant events). In task neuroimaging
studies, the reward network showed enhanced activation
levels when, compared to controls, addicted individuals
were exposed to drug cues (Filbey et al., 2016; Hong et al.,
2017; Kim et al., 2014; Kober et al., 2016; Li et al., 2012,
2015; Ray et al., 2015; Tabatabaei-Jafari et al., 2014),
providing evidence for an increased incentive value of drug
cues to drug users. In contrast, studies that used gambling
paradigms in drug users as compared with controls found
reduced activation levels of the reward network during gain
anticipation (Luijten et al., 2017), as well as during loss
anticipation and realization of monetary loss (Gowin et al.,
2017; Gradin et al., 2014; Worhunsky et al., 2017), sug-
gesting reduced incentive value of monetary rewards and
losses in drug addiction. Studies employing social-
emotional stimuli to provoke an affective reaction simi-
larly demonstrated a blunted reward network response in
addicted individuals (Asensio et al., 2010; Caldwell et al.,
2015; Canterberry et al., 2016; Costumero et al., 2017;
Hong et al., 2017; Seo et al., 2013; Wesley et al., 2016),
further indicating that the incentive value of nondrug-
related stimuli may be decreased in drug addiction. Taken
together, these findings suggest a shift of incentive value
away from nondrug rewards and toward drug-related cues
across addicted populations, as proposed by the iRISA
model. Importantly, this shift in incentive value was
stronger in drug-addicted individuals who had used drugs
more frequently and for longer durations, in general man-
ifesting more severe addiction, suggesting that these
changes may be a direct consequence of drug use (Zilver-
stand et al., 2018). Stronger abnormalities in the activation
levels of the reward network were also linked to a greater
likelihood of relapse in drug users seeking to remain
abstinent (Li et al., 2015; Seo et al., 2013), indicating that
the incentive value shift toward drug-related stimuli con-
tributes to the maintenance of drug seeking and taking in
human drug addiction. Finally, treatment of individuals
with drug addiction led to a reduction of abnormalities in
the reward network (Zilverstand et al., 2016), suggesting
such behavioral and neural normalizations may be a treat-
ment target, potentially reducing drug use and enhancing
abstinence.
A second network shown to have abnormal brain
function in drug addiction is the salience network, which
encompasses the insula, dorsal anterior cingulate cortex,
and inferior parietal cortex. This network integrates inter-
oceptive information with external inputs to detect salient
events, controlling the allocation of attentional control to-
ward them. Similar to the reward network, the salience
network was found to be hyperengaged when drug users
were confronted with drug-related stimuli (Kühn and Gal-
linat, 2011; Zilverstand et al., 2018) and hypoengaged
when drug users were anticipating monetary gains (Luijten
et al., 2017) or anticipating or realizing monetary loss in
gambling tasks (Gowin et al., 2017; Gradin et al., 2014;
Stewart et al., 2014; Wesley et al., 2011) or when they were
confronted with social-emotional stimuli in emotion prov-
ocation task designs (Asensio et al., 2010; Costumero et al.,
2017; Gilman et al., 2010; Hong et al., 2017; Landi et al.,
2011; Maurage et al., 2012; Seo et al., 2013). Beyond the
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Haste thee, nymph, and bring with thee
Jest and youthful Jollity,
Quips and cranks and wanton wiles,
Nods and becks and wreathèd smiles
Such as hang on Hebe’s cheek,
And love to live in dimples sleek,—
Sport that wrinkled Care derides,
And Laughter holding both his sides.
Come, and trip it, as ye go,
On the light fantastic toe;
And in thy right hand lead with thee
The mountain nymph, sweet Liberty:
And, if I give thee honor due,
Mirth, admit me of thy crew,
To live with her, and live with thee,
In unreproved pleasures free.

FROM IL PENSEROSO
By John Milton

Oft, on a plat of rising ground,

I hear the far-off curfew sound
Over some wide watered shore,
Swinging slow with sullen roar;
Or, if the air will not permit,
Some still removed place will fit,
Where glowing embers through the room
Teach light to counterfeit a gloom.

THE LOTOS-EATERS
By Alfred Tennyson

The Lotos blooms below the barren peak:

The Lotos blows by every winding creek:
All day the wind breathes low with mellower tone:
Through every hollow cave and alley lone
Round and round the spicy downs the yellow Lotus-dust is blown.
We have had enough of action, and of motion we,
Rolled to starboard, rolled to larboard, when the surge was seething
free,
Where the wallowing monster spouted his foam-fountains in the sea.
Let us swear an oath, and keep it with an equal mind,
In the hollow Lotus-land to live and lie reclined
On the hills like gods together, careless of mankind.
For they lie beside their nectar, and the bolts are hurled
Far below them in the valleys, and the clouds are lightly curled
Round their golden houses, girdled with the gleaming world;
Where they smile in secret, looking over wasted lands,
Blight and famine, plague and earthquake, roaring deeps, and fiery
sands,
Clanging fights, and flaming towns, and sinking ships, and praying
hands.
But they smile, they find a music centered in a doleful song
Steaming up, a lamentation and an ancient tale of wrong,
Like a tale of little meaning, though the words are strong;
Chanted from an ill-used race of men that cleave the soil,
Sow the seed, and reap the harvest with enduring toil,
Storing yearly little dues of wheat, and wine, and oil;
Till they perish and they suffer—some, ’tis whispered—down in hell
Suffer endless anguish, others in Elysian valleys dwell,
Resting weary limbs at last on beds of asphodel.
Surely, surely, slumber is more sweet than toil, the shore
Than labor in the deep mid-ocean, wind and wave and oar;
O rest ye, brother mariners, we will not wander more.

HOME, WOUNDED
By Sydney Dobell

Blare the trumpet, and boom the gun,

But, O, to sit here thus in the sun,
To sit here, feeling my work is done,
While the sands of life so golden run,
And I watch the children’s posies,
And my idle heart is whispering,
“Bring whatever the years may bring,
The flowers will blossom, the birds will sing,
And there’ll always be primroses.”

THE MINARET BELLS

By William M. Thackeray

Tink a tink, tink a tink,

By the light of the star,
On the blue river’s brink,
I heard a guitar.

I heard a guitar
On the blue waters clear,
And knew by its music
That Selim was near!

Tink a tink, tink a tink,

How the soft music swells,
And I hear the soft clink
Of the minaret bells!

SPRINGTIME
By Leonard G. Nattkemper

May-time’s Spring-time,
O let us steal away.
Spring-time’s love-time,
So let us go to-day.

Oh! the dawn, while dew is on,

Awakes a fragrant breeze;
It fills my room with rich perfume
From snow-white locust trees.

Across the grain there floats a strain

Of ancient witchery;
A robin’s throat hath freed a note
Of rarest ecstasy.

And while he sings, within me springs

An echo to his lay—
But how can words e’er match this bird’s
Sweet song of Spring, I pray!

Such noon-day dreams by babbling streams,

There’s nothing to compare;
Soft zephyrs blow where waters flow,
Entangling my hair.

In shady nooks, fond lover looks

In eyes as blue as skies;
And her reply, though quaint and shy,
Is what true love implies.

So May-time’s Spring-time,
Now let us steal away;
Spring-time’s love-time,
And let us go to-day.

A SINGING LESSON
By Jean Ingelow

A nightingale made a mistake—

She sang a few notes out of tune—
Her heart was ready to break,
And she hid away from the moon.
She wrung her claws, poor thing,
But was far too proud to weep;
She tucked her head under her wing,
And pretended to be asleep.

A lark, arm-in-arm with a thrush,

Came sauntering up to the place;
The nightingale felt herself blush,
Though feathers hid her face.
She knew they had heard her song,
She felt them snicker and sneer;
She thought this life was too long,
And wished she could skip a year.

“Oh, nightingale,” cooed a dove,

“Oh, nightingale, what’s the use?
You bird of beauty and love,
Why behave like a goose?
Don’t skulk away from our sight
Like a common contemptible fowl;
You bird of joy and delight,
Why behave like an owl?

“Only think of all you have done—

Only think of all you can do;
A false note is really fun
From such a bird as you!
Lift up your proud little crest;
Open your musical beak;
Other birds have to do their best,
But you need only speak.”

The nightingale shyly took

Her head from under her wing,
And giving the dove a look
Straightway began to sing.
There was never a bird could pass—
The night was divinely calm—
And the people stood on the grass
To hear that wonderful psalm.
The nightingale did not care—
She only sang to the skies;
Her song ascended there,
And there she fixed her eyes.
The people who listened below
She knew but little about—
And this tale has a moral, I know,
If you’ll try to find it out.

MORAL
Never give up, always look up.
Cheer the discouraged.
Strive for heavenly applause.
Care not for the praise of men, but for the praise of God.

THE WOLVES OF THE SEA

By Herbert Bashford

From dusk until dawn they are hurrying on,

Unfettered and fearless they flee;
From morn until eve they plunder and thieve—
The hungry, white wolves of the Sea!

With never a rest, they race to the west,

To the Orient’s rim do they run;
By the berg and the floe of the northland they go
And away to the isles of the sun.

They wail at the moon from the desolate dune

Till the air has grown dank with their breath;
They snarl at the stars from the treacherous bars
Of the coasts that are haunted by Death.

They grapple and bite in a keen, mad delight

As they feed on the bosom of Grief;
And one steals away to a cave with his prey,
And one to the rocks of the reef.

With the froth on their lips they follow the ships,

Each striving to lead in the chase;
Since loosed by the hand of the King of their band
They have known but the rush of the race.

They are shaggy and old, yet as mighty and bold

As when God’s freshest gale set them free;
Not a sail is unfurled in a part of the world
But is prey for the wolves of the Sea!

—Copyright by Harr Wagner Co., San Francisco, and used by kind

permission of author and publisher.

OLD IRONSIDES
By Oliver Wendell Holmes

Ay, tear her tattered ensign down!

Long has it waved on high,
And many an eye has danced to see
That banner in the sky;
Beneath it rung the battle shout,
And burst the cannon’s roar;—
The meteor of the ocean air
Shall sweep the clouds no more.

Her deck, once red with hero’s blood,

Where knelt the vanquished foe,
When winds were hurrying o’er the flood,
And waves were white below,
No more shall feel the victor’s tread,
Or know the conquered knee;
The harpies of the shore shall pluck
The eagle of the sea!
Oh, better that her shattered hulk
Should sink beneath the wave;
Her thunders shook the mighty deep,
And there should be her grave;
Nail to the mast her holy flag,
Set every threadbare sail,
And give her to the god of storms,
The lightning and the gale!

COLUMBUS
By Joaquin Miller

Behind him lay the gray Azores,

Behind the Gates of Hercules;
Before him not the ghost of shores;
Before him only shoreless seas.
The good mate said: “Now must we pray,
For lo! the very stars are gone.
Brave Adm’r’l, speak; what shall I say?”
“Why, say: ‘Sail on! sail on! and on!’”

“My men grow mutinous day by day;

My men grow ghastly wan and weak.”
The stout mate thought of home; a spray
Of salt wave washed his swarthy cheek.
“What shall I say, brave Adm’r’l, say,
If we sight naught but seas at dawn?”
“Why, you shall say at break of day:
‘Sail on! Sail on! Sail on! and on!’”

They sailed and sailed, as winds might blow,

Until at last the blanched mate said:
“Why, now, not even God would know
Should I and all my men fall dead.
These very winds forget their way;
For God from these dread seas is gone.
Now speak, brave Adm’r’l; speak and say—”
He said: “Sail on! sail on! and on!”

They sailed: they sailed. Then spake the mate:

“This mad sea shows his teeth to-night,
He curls his lip, he lies in wait,
With lifted teeth, as if to bite!
Brave Adm’r’l, say but one good word:
What shall we do when hope is gone?”
The words leapt like a leaping sword:
“Sail on! Sail on! Sail on! and on!”

Then pale and worn, he kept his deck,

And peered through darkness. Ah, that night
Of all dark nights! And then a speck—
A light! A light? A light! A light!
It grew; a starlit flag unfurled!
It grew to be Time’s burst of dawn.
He gained a world; he gave that world
Its grandest lesson: “On! sail on!”

—Copyright by Harr Wagner Co., San Francisco, and used by kind

permission of author and publisher.

DAYBREAK
By Robert Browning

Day!
Faster and more fast,
O’er night’s brim, day boils at last:
Boils pure gold, o’er the cloud-cup’s brim
Where spurting and suppressed it lay,
For not a froth-flake touched the rim
Of yonder gap in the solid gray
Of the eastern cloud, an hour away;
But forth one wavelet, then another, curled,
Till the whole sunrise, not to be suppressed,
Rose, reddened, and its seething breast
Flickered in bounds, grew gold, then overflowed the world.

Oh, Day, if I squander a wavelet of thee,

A mite of my twelve hours’ treasure,
The least of thy gazes or glances,
(Be they grants thou art bound to or gifts above measure)
One of thy choices or one of thy chances,
(Be they tasks God imposed thee or freaks at thy pleasure)
—My Day, if I squander such labor or leisure,
Then shame fall on Asolo, mischief on me!

Thy long, blue, solemn hours serenely flowing,

Whence earth, we feel, gets steady help and good—
Thy fitful sunshine-minutes, coming, going,
As if earth turned from work in gamesome mood—
All shall be mine! But thou must treat me not
As prosperous ones are treated, those who live
At hand here, and enjoy the higher lot,
In readiness to take what thou wilt give,
And free to let alone what thou refusest;
For, Day, my holiday, if thou ill-usest
Me, who am only Pippa,—old-year’s sorrow,
Cast off last night, will come again to-morrow:
Whereas, if thou prove gentle, I shall borrow.
Sufficient strength of thee for new-year’s sorrow.
All other men and women that this earth
Belongs to, who all days alike possess,
Make general plenty cure particular dearth,
Get more joy one way, if another, less:
Thou art my single day, God lends to leaven
What were all earth else, with a feel of heaven.

—From “Pippa Passes.”

MY SWORD SONG
 By Richard Realf

Day in, day out, through the long campaign,

I march in my place in the ranks;
And whether it shine or whether it rain,
My good sword cheerily clanks;
It clanks and clanks in a knightly way
Like the ring of an armored heel;
And this is the song which day by day,
It sings with its lips of steel:

“O friend, from whom a hundred times,

I have felt the strenuous grip
Of the all-renouncing love that climbs
To the heights of fellowship;
Are you tired of all the weary miles?
Are you faint with your swooning limbs?
Do you hunger back for the olden smiles,
And the lilt of olden hymns?

“Has your heart grown weak since that rapt hour

When you leapt, with a single bound,
From dreaming ease to sovereign power
Of a living soul world-crowned?
Behold! the aloes of sacrifice
Are better than radiant wine,
And the bloody sweat of a cause like this
Is an agony divine.

“Under the wail of the shuddering world

Amoan for its fallen sons;
Over the volleying thunders hurled
From the throats of the wrathful guns;
Above the roar of the plunging line
That rocks with the fury of hell,
Runs the absolute voice: O Earth of mine,
Be patient, for all is well!”
Thus sings my sword to my soul, and I,
Albeit the way is long,
As soiled clouds darken athwart the sky—
Still keep my spirit strong:
Whether I live, or whether I lie
On the stained ground, ghastly and stark,
Beyond the carnage I shall descry
God’s love shines across the dark.

—Copyright by Funk & Wagnalls Co., New York, and used by their
kind permission.

LABOR
Anonymous

Toil swings the ax, and forests bow;

The seeds break out in radiant bloom,
Rich harvests smile behind the plow,
And cities cluster round the loom;
Where towering domes and tapering spires
Adorn the vale and crown the hill,
Stout labor lights its beacon-fires,
And plumes with smoke the forge and mill.

The monarch oak, the woodland’s pride,

Whose trunk is seamed with lightning scars,
Toil launches on the restless tide,
And there unrolls the flag of stars;
The engine with its lungs of flame,
And ribs of brass and joints of steel,
From Labor’s plastic fingers came,
With sobbing valve and whirling wheel.

’Tis Labor works the magic press,

And turns the crank in hives of toil,
And beckons angels down to bless
 Industrious hands on sea and soil.
Here sun-brown Toil, with shining spade,
Links lake to lake with silver ties
Strung thick with palaces of trade,
And temples towering to the skies.

THE ARROW AND THE SONG[17]

By Henry W. Longfellow

I shot an arrow into the air,

It fell to earth, I knew not where;
For, so swiftly it flew, the sight
Could not follow it in its flight.

I breathed a song into the air,

It fell to earth, I knew not where;
For who has sight so keen and strong,
That it can follow the flight of song?

Long, long afterward, in an oak

I found the arrow, still unbroke;
And the song, from beginning to end,
I found again in the heart of a friend.

THE BELLS OF SAN GABRIEL

By Charles Warren Stoddard
[Particularly note the possibility of onomatopoesy in the following
refrain. What answer do the bells give to the questions of the poet?
There is no other answer than their steady, monotonous toll. The
answer must be found in your own heart, viz., that no good work,
done with high zeal and enthusiasm, with self-sacrifice, ever can be
in vain. Then read the refrain as a bell would sound, if it were struck
at the end of each line, prolonging the sound to correspond with the
continued resonance of the bell.]
Thine was the corn and the wine,
The blood of the grape that nourished;
The blossom and fruit of the vine
That was heralded far away.
These were thy gifts; and thine,
When the vine and the fig-tree flourished,
The promise of peace and of glad increase
Forever and ever and aye.
What then wert thou, and what art now?
Answer me, O, I pray!

And every note of every bell

Sang Gabriel! rang Gabriel!
In the tower that is left the tale to tell
Of Gabriel, the Archangel.

Oil of the olive was thine;

Flood of the wine-press flowing;
Blood o’ the Christ was the wine—
Blood o’ the Lamb that was slain.
Thy gifts were fat o’ the kine
Forever coming and going
Over the hills, the thousand hills,
Their lowing a soft refrain.
What then wert thou, and what art now?
Answer me, once again!

And every note of every bell

Sang Gabriel! rang Gabriel!
In the tower that is left the tale to tell
Of Gabriel, the Archangel.

Seed o’ the corn was thine—

Body of Him thus broken
And mingled with blood o’ the vine—
The bread and the wine of life;
Out of the good sunshine
They were given to thee as a token—
The body of Him, and the blood of Him,
When the gifts of God were rife.
What then wert thou, and what art now,
After the weary strife?

And every note of every bell

Sang Gabriel! rang Gabriel!
In the tower that is left the tale to tell
Of Gabriel, the Archangel.

Where are they now, O bells?

Where are the fruits o’ the Mission?
Garnered, where no one dwells.
Shepherd and flock are fled.
O’er the Lord’s vineyard swells
The tide that with fell perdition
Sounded their doom and fashioned their tomb
And buried them with the dead.
What then wert thou, and what art now?—
The answer is still unsaid.

And every note of every bell

Sang Gabriel! rang Gabriel!
In the tower that is left the tale to tell
Of Gabriel, the Archangel.

Where are they now, O tower!

The locusts and wild honey?
Where is the sacred dower
That the bride of Christ was given?
Gone to the builders of power,
The misers and minters of money;
Gone for the greed that is their creed—
And these in the land have thriven.
What then wert thou, and what art now,
And wherefore hast thou striven?

And every note of every bell

 Sang Gabriel! rang Gabriel!
In the tower that is left the tale to tell
Of Gabriel, the Archangel.

—Copyright by John Lane, New York, and used by kind

permission.

A WELCOME TO ALEXANDRA
March 7, 1863
By Alfred, Lord Tennyson

Sea-kings’ daughter from over the sea, Alexandra!

Saxon and Norman and Dane are we,
But all of us Danes in our welcome of thee, Alexandra!
Welcome her, thunders of fort and of fleet!
Welcome her, thundering cheer of the street!
Welcome her, all things youthful and sweet,
Scatter the blossoms under her feet!
Break, happy land, into earlier flowers!
Make music, O bird, in the new-budded bowers!
Blazon your mottoes of blessing and prayer!
Welcome her, welcome her, all that is ours!
Warble, O bugle, and trumpet, blare!
Flags, flutter out upon turrets and towers!
Flames, on the windy headland flare!
Utter your jubilee, steeple and spire!
Clash, ye bells, in the merry March air!
Flash, ye cities, in rivers of fire!
Rush to the roof, sudden rocket, and higher
Melt into stars for the land’s desire!
Roll and rejoice, jubilant voice,
Roll as a ground-swell dash’d on the strand,
Roar as the sea when he welcomes the land,
And welcome her, welcome the land’s desire.
The sea-kings’ daughter is happy as fair,
Blissful bride of a blissful heir,
Bride of the sire of the kings of the sea—
O joy to the people and joy to the throne,
Come to us, love us and make us your own;
For Saxon or Dane or Norman we,
Teuton or Celt, or whatever we be,
We are each all Dane in our welcome of thee, Alexandra!

CHRISTMAS IN INDIA
By Rudyard Kipling

Dim dusk behind the tamarisks—the sky is saffron yellow—

As the women in the village grind the corn,
And the parrots seek the river-side, each calling to his fellow
That the Day, the staring Eastern Day is born.
Oh, the white on the highway! Oh, the stenches in the byway!
Oh, the clammy fog that hovers over earth!
And at home they’re making merry ’neath the white and scarlet berry
—
What part have India’s exiles in their mirth?

Full day behind the tamarisks—the sky is blue and staring—

As the cattle crawl afield beneath the yoke,
And they bear one o’er the field path, who is past all hope or caring,
To the ghat below the curling wreaths of smoke.
Call on Rama, going slowly, as ye bear a brother slowly—
Call on Rama—he may hear, perhaps, your voice!
With our hymn-books and our psalters we appeal to other altars,
And to-day we bid good Christian men rejoice!

High noon behind the tamarisks—the sun is hot above us—

As at home the Christmas Day is breaking wan,
They will drink our healths at dinner—those who tell us how they
love us,
And forget us till another year be gone!
Oh, the toil that knows no breaking! Oh, the Heimweh, ceaseless,
aching!
 Oh, the black dividing sea and alien plain.
Youth was cheap, wherefore we sold it.
Gold was good—we hoped to hold it,
And to-day we know the fullness of our gain.

Gray dusk behind the tamarisks—the parrots fly together—

As the sun is sinking slowly over Home;
And the last ray seems to mock us shackled in a lifelong tether
That drags us back howe’er so far we roam.
Hard her service, poor her payment—she in ancient, tattered
raiment—
India, she the grim stepmother of our kind.
If a year of life be lent her, if her temple’s shrine we enter,
The door is shut—we may not look behind.

Black night behind the tamarisks—the owls begin their chorus—

As the conches from the temple scream and bray.
With fruitless years behind us, and the hopeless years before us,
Let us honor, O my brothers, Christmas Day!
Call a truce, then, to our labors—let us feast with friends and
neighbors,
And be merry as the custom of our caste;
For if “faint and forced the laughter,” and if sadness follow after,
We are richer by one mocking Christmas past.

THE BELLS OF SHANDON

By Francis Mahony

With deep affection

And recollection
I often think of
Those Shandon bells,
Whose sound so wild would,
In the days of childhood,
Fling round my cradle
Their magic spells.
On this I ponder
Where’er I wander,
And thus grow fonder,
Sweet Cork, of thee—
With thy bells of Shandon
That sound so grand on
The pleasant waters
Of the River Lee.

I’ve heard bells chiming

Full many a clime in,
Tolling sublime in
Cathedral shrine;
While at a glib rate
Brass tongues would vibrate;
But all their music
Spoke naught like thine.

For memory, dwelling

On each proud swelling
Of thy belfry, knelling
Its bold notes free,
Made the bells of Shandon
Sound far more grand, on
The pleasant waters
Of the River Lee.

I’ve heard bells tolling

Old Adrian’s Mole in
Their thunder rolling
From the Vatican;
And cymbals glorious
Swinging uproarious
In the gorgeous turrets
Of Notre Dame;

But thy sounds were sweeter

Than the dome of Peter
Flings o’er the Tiber,
Pealing solemnly.
O, the bells of Shandon
Sound far more grand, on
The pleasant waters
Of the River Lee.

There’s a bell in Moscow

Where on tower and kiosko
In Saint Sophia
The Turkman gets,
And loud in air
Calls men to prayer,
From the tapering summits
Of tall minarets.

Such empty phantom

I freely grant them;
But there’s an anthem
More dear to me;
’Tis the bells of Shandon
That sounds so grand, on
The pleasant waters
Of the River Lee.

THE DAY AND THE WORK

By Edwin Markham

To each man is given a day and his work for the day;
And once, and no more, he is given to travel this way.
And woe if he flies from the task, whatever the odds;
For the task is appointed to him on the scroll of the gods.

There is waiting a work where only your hands can avail;

And so if you falter, a chord in the music will fail.
We may laugh to the sky, we may lie for an hour in the sun;