Neuroimaging in Addiction

Bryon Adinoff, Elliot A. Stein, Bryon Adinoff, Elliot A. Stein

• Publisher: Wiley
• Year: 2011
• ISBN:
  9781119972709
• Edition: 1
• Topic: Medicine
• Subtopic: Psychiatry & Mental Health

Neuroimaging in Addiction presents an up-to-date, comprehensive review of the functional and structural imaging human studies that have greatly advanced our understanding of this complex disorder. Approaching addiction from a conceptual rather than a substance-specific perspective, this book integrates broad neuropsychological constructs that consider addiction as a neuroplastic process with genetic, developmental, and substance-induced contributions.

The internationally recognized contributors to this volume are leaders in clinical imaging with expertise that spans the addiction spectrum.

Following a general introduction, an overview of neural circuitry and modern non-invasive imaging techniques provides the framework for subsequent chapters on reward salience, craving, stress, impulsivity and cognition. Additional topics include the use of neuroimaging for the assessment of acute drug effects, drug-induced neurotoxicity, non-substance addictive behaviors, and the application of imaging genetics to identify unique intermediate phenotypes. The book concludes with an exploration of the future promise for functional imaging as guide to the diagnosis and treatment of addictive disorders.

Scientists and clinicians will find the material in this volume invaluable in their work towards understanding the addicted brain, with the overall goal of improved prevention and treatment outcomes for patients.

Features a Foreword by Edythe London, Director of the Center for Addictive Behaviors, University of California at Los Angeles.

Chapter 1

Introduction

Bryon Adinoff1,2 and Elliot Stein3

1Department of Psychiatry, UT Southwestern Medical Center, Dallas, TX

2VA North Texas Health Care System, Dallas, TX

3National Institutes on Drug Abuse-Intramural Research Program, Baltimore, MD

Derived from addictionem, meaning “an awarding, a devoting,” the term addiction evolved in the 1600s to suggest a tendency of habits and pursuits. Used in the modern sense since the 1800s with reference to tobacco, opium, and spirits, addiction now describes a symptom complex of loss of control, compulsive use, and continued use despite adverse consequence. Although “dependence” was used by DSM III to describe the physical dependence upon drugs and alcohol (as evidenced by tolerance and withdrawal) and subsequently by DSM III-R and IV to include the three Cs (Control, Compulsive use, and Consequences), there is now relatively widespread agreement that “addiction” best denotes the symptom cluster that is the focus of this volume: Neuroimaging in Addiction [1]. As this book goes to press, the DSM-V work group on substance-related disorders has recommended that “addiction” replace “dependence” as the diagnostic label that defines these behaviors, concerns regarding its vagueness, associated stigma, overuse, and non-scientific formulation non-withstanding [2].

“Addiction,” however, has also been usurped in the public domain to describe any behavior that is performed in excess, including Internet use, sex, chocolate, shopping, pornography, gambling, tanning, or eating. Whether or not these behaviors are truly “addictive,” and whether these behaviors are consistent with a disease process, begs the question of how to definitively identify this disorder. The diagnosis of substance use disorders (in addition to other so-called “process” or “behavioral” addictions), unfortunately, shares a dilemma encountered throughout psychiatry – the diagnosis is based solely on descriptive, symptomatic checklist criteria. The use of biological measures, such as blood tests, physiological measures (e.g., blood pressure), electrocardiograms, or x-rays, to diagnosis disease states, which are standard protocol throughout the rest of medicine, continues to elude our field. The absence of accurate (or even partially accurate) biological markers to guide the diagnosis of neuropsychiatric disorders remains a critical limiting factor in discerning a neurobiologically-based disease from a non-pathological behavioral state and may, in part, be responsible for the poor outcome prognoses for many of our patients suffering from addiction. We believe that neuroimaging techniques offer the best hope to realize this Holy Grail of psychiatry.

When the editors began their training, brain imaging was in its early stages of development and implementation as a diagnostic tool. Researchers and clinicians were suddenly provided the opportunity to safely, and with relatively minimal patient discomfort, investigate the human brain in situ. The promises inspired by structural and functional brain imaging were profound. The 1990s were pronounced “The Decade of the Brain” and it was assumed that these tools would herald the neurobiologically based diagnosis and targeted treatment of psychiatric disorders by the turn of the twenty-first century. This, of course, did not happen. What did happen, however, were stunning technical advancements in assessing brain activity that allowed an unparalleled investigation of neural processes, exponentially increasing our understanding of how the brain perceives, integrates, and responds to sensory and affective stimuli. Steady progress has also been evident in unveiling the neurobiological differences in individuals with psychiatric disorders, albeit not (as of yet) with the diagnostic sensitivity and specificity required for clinical use. These advances, perhaps most impressive in the addictive disorders, has motivated the publication of Neuroimaging in Addiction.

The accomplishments in understanding the neural processes involved in addiction are due, at least in part, to superb animal models that closely mimic the repetitive and compulsive drug-taking behaviors observed in addicted humans. Neuroimaging techniques have provided the interface necessary to translate these anatomical, cellular and circuitry models into the human addicted brain. A major accomplishment of these closely aligned approaches is the elucidation of biologic processes that are shared across several substances of abuse. The growing confluence of these two approaches signaled to the editors that the timing was propitious to summarize the neuroimaging findings to-date and has guided two key concepts encapsulated in Neuroimaging in Addiction.

First, the chapters have been organized by key constructs shared across the various substances of abuse, starting with a description of shared disruptions in neurocircuitry and extending to experiential, cognitive and behavioral processes such as reward salience, craving, stress, and impulsivity. This approach, rather than a categorical approach based upon a specific drug of abuse, supports the common DSM-IV behavioral criteria used to describe all additive disorders. Second, the title of the book refers to Addiction in the singular, denoting a common disease process that is differentially manifested (i.e., a shared etiology and neurocircuitry that is variably expressed with different drug choices) rather than a spectrum disorder (i.e., each substance addiction encapsulates its own etiologic and biologic profile with shared symptoms across each substance). This distinction has critical implications for our understanding, as well as treatment, of addiction.

Guided by this framework, the contributors to Neuroimaging in Addiction detail the state-of-the-art in their respective fields. Although the original intent of the editors was to specifically highlight the advances of neuroimaging in addiction, each chapter has also evolved into a superb overview of the construct or topic approached and thus simultaneously provides the reader with an excellent textbook on addiction neurobiology. This extensive overview emphasizes the remarkable progress that has occurred in our field over the past ten years.

Yet, as noted earlier, these great leaps forward have not been paralleled with similar progress in the diagnosis or treatment of addiction. Making accurate diagnoses on an individual subject/patient basis remains elusive, as does our ability to assess treatment efficacy. Nevertheless, dramatic advances in imaging technology, coupled with those in other fields (e.g., genomics, drug discovery), promise such breakthroughs in the not-too-distant future. New technologies have and will continue to offer new insights in the structure and function of both the healthy brain and its pathophysiology. Justified excitement in the neuroimaging field can be seen in the recent advances in the ability to perform white matter tract tracing in situ, combine the excellent temporal resolution of EEG with the superb spatial resolution of fMRI in combined recording studies, and measure the important neurotransmitters glutamate and GABA via MR spectroscopy. New PET ligands are starting to emerge from the lab, promising the ability to make molecular measurements of compounds based on scientific hypotheses, not simply because a ligand was available. And new hardware continues to be developed, whether it be ever higher field MRI scanners (a human 11.7 T scanner is currently in development) or the exciting recent PET camera insert into a standard 3T MRI, allowing for the first time simultaneous measurements. Finally, especially in the field of MRI, new analysis methods are continually being developed to better extract information from the rich MRI signal. These developments include the rapidly evolving field of resting state functional connectivity, and its analysis using network and multivariate analyzes, although only the former has yet to be applied to the addiction field.

Elucidating subject-specific differences in brain functioning will enable the identification of neural correlates of behavioral complexes, unique intermediate phenotypes, and/or substance-specific disruptions as well as targeted treatment approaches and objective assessments of treatment efficacy. Clarification of the distinct and overlapping neural networks defining addictive and other psychiatric disorders, including schizophrenia, bipolar, post-traumatic stress, and antisocial social personality disorders, will allow increasingly focused treatment approaches. Finally, it is likely that identifying neural signatures of addiction will markedly diminish the stigma associated with addictive disorders. Such biological markers should lessen the fear and shame that accompanies this disease, and in turn, remove self-imposed, social, and medical obstacles in seeking and obtaining treatment. It is our hope that scientists, clinicians, and students will find the material in this volume useful as we continue our journey to understand the addicted brain with the goal of improved prevention and treatment outcomes for our patients.

References

1. O’Brien, C.P., Volkow, N., and Li, T.K. (2006) What's in a word? Addiction versus dependence in DSM-V. American Journal of Psychiatry, 163, 764–765.

2. Erickson, C.K. (2007) Terminology and characterization of “Addiction”, in The Science of Addiction: From Neurobiology to Treatment, W. W. Norton & Company, New York, pp. 1–31.

Chapter 2

An Integrated Framework for Human Neuroimaging Studies of Addiction from a Preclinical Perspective

Karen D. Ersche1 and Trevor W. Robbins1,2

1University of Cambridge, Behavioural & Clinical Neuroscience Institute, Cambridge, UK

2University of Cambridge, Department of Experimental Psychology, Cambridge, UK

2.1 Introduction

Preclinical research into the neural substrates of drug dependence focused attention onto the dopamine-dependent functions of the nucleus accumbens of the ventral striatum in rewarded behavior (see recent review [1]. More recent analyzes have shown the importance of considering the neural context of the ventral striatum in subserving such behavior [2], including limbic-cortical and prefrontal interactions with the striatum. It is this framework of preclinical research that has guided the yet more complex issues of the neural substrates of addiction, particularly in humans, to a variety of drugs of abuse, including stimulants and opiates.

2.2 A Conceptual Framework for Understanding Drug Addiction Based on Preclinical Observations

Understanding the neural basis of drug addiction has required an integrated approach from both studies in cognitive and affective neuroscience on human volunteers and clinical patients, and also from behavioral neuroscientists and psychopharmacologists conducting well-controlled animal experiments. However, it was discoveries derived from experiments with animals that provided the first clues about how the brain might mediate reinforcement processes relevant to addiction, and it is this literature that underpins many of today's sophisticated investigations of the neural substrates of human addiction. Perhaps the seminal discovery was that by Roberts et al. [3], who showed that depleting dopamine from the mesolimbic dopamine system appeared to block the self-administration of intravenous cocaine in rats in a way that could not easily be accounted for as a motor deficit (given the implication of dopamine in Parkinson's disease). Previous work by several groups beginning with Crow [4] had implicated mesolimbic dopamine in a “brain reward system” from studies on intracranial self-stimulation via implanted electrodes in the medial forebrain bundle.

2.2.1 The Pivotal Role of the Nucleus Accumbens

One of the terminal regions of the mesolimbic dopamine system is a structure in the basal forebrain, associated with both the basal ganglia and the limbic system, the nucleus accumbens. Much interest was already focused on the role of the nucleus accumbens in reward processes when Hoebel et al. [5] showed that rats would self-administer d-amphetamine directly into this region unilaterally in very small volumes – with little evidence of other “hot-spots.” Phillips et al. [6] confirmed this finding with evidence from bilateral self-administered infusions that were up-regulated by simultaneously adding dopamine D1 or D2 receptor antagonists to the infusate – suggesting that the rats were “regulating” their preferred level of dopamine receptor stimulation, as rates of self-administration increased, again contrary to what would be expected of a purely motor function for these neurons.

Two other classic studies have confirmed an important focus on dopamine-dependent functions of the nucleus accumbens, while broadening its involvement to include non-stimulant drugs such as heroin and alcohol. DiChiara and Imperato [7], using in vivo microdialysis, have shown that many drug withdrawal states, whether from stimulants such as co...

Table of contents

• Cover
• Title Page
• Copyright
• Dedication
• Foreword
• List of Contributors
• Chapter 1: Introduction
• Chapter 2: An Integrated Framework for Human Neuroimaging Studies of Addiction from a Preclinical Perspective
• Chapter 3: Structural and Functional Neuroimaging Methods: Applications to Substance Abuse and Addiction
• Chapter 4: Functional Neuroimaging of the Acute Effects of Drugs of Abuse
• Chapter 5: Reward Processing
• Chapter 6: A Neuroimaging Approach to the Study of Craving
• Chapter 7: Impulsivity and Addiction
• Chapter 8: Cognitive Disruptions in Drug Addiction: a Focus on the Prefrontal Cortex
• Chapter 9: Neural Mechanisms of Stress and Addiction
• Chapter 10: Anatomical and Neurochemical Evidence of Neurotoxic Changes in Psychostimulant Abuse and Dependence
• Chapter 11: Neuroimaging in Behavioral Addictions
• Chapter 12: Imaging Genetics and Addiction
• Chapter 13: The Diagnostic and Therapeutic Potential of Neuroimaging in Addiction Medicine
• Index