Praise for The Compass of Pleasure
“In his book The Compass of Pleasure, the Johns Hopkins neurobiologist David J. Linden explicates the workings of [the regions of the brain] known collectively as the reward system, elegantly drawing on sources ranging from personal experience to studies of brain activity to experiments with molecules and genes.”
—The New York Times Book Review
“Important, timely, and fascinating.”
—Naomi Wolf, author of The Shock Doctrine, The Beauty Myth, and The End of America
“[H]ugely entertaining . . . If you’re science-phobic, don’t worry: Linden is incredibly smart, but comes across as the funny, patient professor you wish you’d had in college.”
—www.npr.org
“How do orgasms, heroin, greasy foods, and juicy gossip jolt the same neurons? Neuroscientist David Linden delves into the research, mixing in plenty of trippy anecdotes.”
—Psychology Today
“Linden’s conversational style, his abundant use of anecdotes, and his successful coupling of wit with insight makes the book a joy to read. Even the footnotes are sprinkled with hidden gems.”
—Publishers Weekly
“Conventional wisdom advises, “If it feels good, stop it. If it tastes good, spit it out.” But why? Because indulging pleasurable excess, whether of drugs, food, or sex, has an unforgiving downside. The biology of how we know this is the topic of Linden’s fascinating, by turns technical and entertaining effort.”
—Donna Chavez, Booklist
“This cheerful summary of the brain’s reward system is a profound experience. . . . Pleasure is a superb book. My brain has been changed by reading it.”
—Leo Benedictus, The Guardian (London)
“This book is highly readable and full of fascinating facts and theories. . . . You’re sure to get pleasure from reading Pleasure.”
—Susan Blackmore, BBC Focus (London)
ABOUT THE AUTHOR
David J. Linden is a professor of neuroscience at The Johns Hopkins University School of Medicine. The author of The Accidental Mind (2007), The Compass of Pleasure (2011), and most recently, Touch (2015), he served for many years as the chief editor of The Journal of Neurophysiology. He lives in Baltimore, Maryland, with his two children.
Praise for The Compass of Pleasure
About the Author
Title Page
Copyright
Dedication
Epigraph
Prologue
CHAPTER ONE Mashing the Pleasure Button
CHAPTER TWO Stoned Again
CHAPTER THREE Feed Me
CHAPTER FOUR Your Sexy Brain
CHAPTER FIVE Gambling and Other Modern Compulsions
CHAPTER SIX Virtuous Pleasures (and a Little Pain)
CHAPTER SEVEN The Future of Pleasure
Acknowledgments
Notes
Index
“Pleasure never comes sincere to man;
but lent by heaven upon hard usury.”
—John Dryden, Edippus
“Phil was probably passed out somewhere, enjoying his dead father’s legacy. I found myself wishing I had a loved one who would die and leave me their barbiturates, but I couldn’t think of anyone who’d ever loved me that much. My uncle had already promised his to the mail lady.”
—Donald Ray Pollock, “Bactine”
PROLOGUE
Bangkok, 1989. The afternoon rains have ended, leaving the early evening air briefly free of smog and allowing that distinctive Thai perfume, frangipani with a faint note of sewage, to waft over the shiny streets. I hail a tuk-tuk, a three-wheel motorcycle taxi, and hop aboard. My young driver has an entrepreneurial smile as he turns around and begins the usual interrogation of male travelers.
“So …you want girl?”
“No.”
“I see.” Long pause, eyebrows slowly raised. “You want boy!”
“Uh, no.”
Longer pause. Sound of engine sputtering at idle. “You want ladyboy?”
“No,” I answer, a bit more emphatically, nonplussed at the idea that I give the impression of desiring this particular commodity.
“I got cheap cigarettes …Johnnie Walker …”
“No thanks.”
Undaunted, he moves on to the next category of his wares, now with lowered voice.
“You want ganja?”
“No.”
“Coke?”
“No.”
“Ya baa [methamphetamine tablets]?”
“Nope.”
A whisper now. “Heroin?”
“No.”
Voice raised back to normal. “I can take you to cockfight. You can gamble!”
“I’ll pass.”
Just a little bit irritated now. “So, farang, what you want?”
“Prik kee noo,” I respond. “Those little ‘mouse shit’ peppers. I want some good, spicy dinner.” My driver, not surprisingly, is disappointed. As we tear through the streets to a restaurant, blasting through puddles, I’m left wondering: Aside from various shades of illegality, what do all his offers have in common? What is it exactly that makes a vice?
We humans have a complicated and ambivalent relationship to pleasure, which we spend an enormous amount of time and resources pursuing. A key motivator of our lives, pleasure is central to learning, for we must find things like food, water, and sex rewarding in order to survive and pass our genetic material to the next generation. Certain forms of pleasure are accorded special status. Many of our most important rituals involving prayer, music, dance, and meditation produce a kind of transcendent pleasure that has become deeply ingrained in human cultural practice.
As we do with most powerful forces, however, we also want to regulate pleasure. In cultures around the world we find well-defined ideas and rules about pleasure that have persisted throughout history in any number of forms and variations:
Pleasure should be sought in moderation.
Pleasure must be earned.
Pleasure must be achieved naturally.
Pleasure is transitory.
The denial of pleasure can yield spiritual growth.
Our legal systems, our religions, our educational systems are all deeply concerned with controlling pleasure. We have created detailed rules and customs surrounding sex, drugs, food, alcohol, and even gambling. Jails are bursting with people who have violated laws that proscribe certain forms of pleasure or who profit by encouraging others to do so.
One can fashion reasonable theories of human pleasure and its regulation using the methods of cultural anthropology or social history. These are valid and useful endeavors, for ideas and practices involving human pleasure are certainly deeply influenced by culture. However, what I’m seeking here in The Compass of Pleasure is a different type of understanding—one less nuanced, perhaps, but more fundamental: a cross-cultural biological explanation. In this book I will argue that most experiences in our lives that we find transcendent—whether illicit vices or socially sanctioned ritual and social practices as diverse as exercise, meditative prayer, or even charitable giving—activate an anatomically and biochemically defined pleasure circuit in the brain. Shopping, orgasm, learning, highly caloric foods, gambling, prayer, dancing ’til you drop, and playing on the Internet: They all evoke neural signals that converge on a small group of interconnected brain areas called the medial forebrain pleasure circuit. It is in these tiny clumps of neurons that human pleasure is felt. This intrinsic pleasure circuitry can also be co-opted by artificial activators like cocaine or nicotine or heroin or alcohol. Evolution has, in effect, hardwired us to catch a pleasure buzz from a wide variety of experiences from crack to cannabis, from meditation to masturbation, from Bordeaux to beef.
This theory of pleasure reframes our understanding of the part of the human body that societies are most intent upon regulating. While we might assume that the anatomical region most closely governed by laws, religious prohibitions, and social mores is the genitalia, or the mouth, or the vocal cords, it is actually the medial forebrain pleasure circuit. As societies and as individuals, we are hell-bent on achieving and controlling pleasure, and it is those neurons, deep in our brains, that are the nexus of that struggle.
These particular neurons also comprise another battleground. The dark side of pleasure is, of course, addiction. It is now becoming clear that addiction is associated with long-lasting changes in the electrical, morphological, and biochemical functions of neurons and synaptic connections within the medial forebrain pleasure circuit. There are strong suggestions that these changes underlie many of the terrifying aspects of addiction, including tolerance (needing successively larger doses to get high), craving, withdrawal, and relapse. Provocatively, such persistent changes appear to be nearly identical to experience-and learning-driven changes in neural circuitry that are used to store memories in other brain regions. In this way, memory, pleasure, and addiction are closely intertwined.
However, addiction is not the only force responsible for experience-driven changes within the brain’s pleasure circuits. The combination of associative learning and pleasure has created nothing less than a cognitive miracle: We can be motivated by pleasure to achieve goals that are entirely arbitrary—goals that may or may not have an evolutionary adaptive value. These can be as wide-ranging as reality-based television and curling. For us humans (and probably for other primates and for cetaceans as well), even mere ideas can activate the pleasure circuit. Our eclecticism where pleasure is concerned serves to make our human existence wonderfully rich and complex.
I like to tell the students in my lab that the golden age of brain research is right now, so it’s time to get down to business. This sounds like a cheap motivational gimmick, but it’s true. Our accumulating understanding of neural function, coupled with enabling technologies that allow us to measure and manipulate the brain with unprecedented precision, has given us new and often counterintuitive insights into behavioral and cognitive phenomena at the levels of biological processes. Nowhere is this more evident than in the neurobiology of pleasure. One example: Do you, like many, think that drug addicts become drug addicts because they derive greater reward from getting high than others? The biology says no: They actually seem to want it more but like it less.
This level of analysis is not only of academic interest. Understanding the biological basis of pleasure leads us to fundamentally rethink the moral and legal aspects of addiction to drugs, food, sex, and gambling and the industries that manipulate these pleasures in the marketplace. It also calls for a reformation in our concepts of such virtuous and prosocial behaviors as sharing resources, self-deprivation, and the drive for knowledge. Crucially, brain imaging studies show that giving to charity, paying taxes, and receiving information about future events all activate the same neural pleasure circuit that’s engaged by heroin or orgasm or fatty foods. Perhaps, most important, analysis of the molecular basis of enduring changes in the brain’s pleasure circuitry holds great promise for developing drugs and other therapies to help people break free of addictions of many sorts, to both substances and experiences.
When I was a postdoctoral fellow at the Roche Institute of Molecular Biology in the early 1990s, I was fortunate to work with Sid Udenfriend, a pioneer in the biochemistry of the brain and a real mensch. Sid’s favorite pedagogical phrase, usually intoned at the bar, was “It’s always good to know a little chemistry.” I couldn’t agree more. It would be possible to write a book exploring the brain’s pleasure circuits that was free of not only molecules but also basic anatomy, but that sort of spoon-feeding would require ignoring some of the most interesting and important issues, and so that’s not what you’ll find here. If you come along for the ride and work with me just a bit to learn some basic neuroscience, I’ll do my best to make it lively and fun as we explore the cellular and molecular basis of human pleasure, transcendent experience, and addiction.
CHAPTER ONE
MASHING THE PLEASURE BUTTON
Montréal, 1953. Fortunately, Peter Milner and James Olds didn’t have perfect aim. While postdoctoral fellows at McGill University, under the direction of the renowned psychologist Donald Hebb, Olds and Milner were conducting experiments that involved implanting electrodes deep in the brains of rats. The implanting surgery, conducted while the animals were anesthetized, involved cementing a pair of electrodes half a millimeter apart to their skulls. After a few days of recovery from the surgery, the rats were fine. Long, flexible wires were then attached to the electrodes at one end and to an electrical stimulator at the other, to allow for activation of the specific brain region where the tips of the electrodes had come to rest.
One fall day Olds and Milner were testing a rat in which they had attempted to target a structure called the midbrain reticular system. Located at the midline of the brain, at the point where its base tapers to form the brain stem, this region had previously been shown by another lab to control sleeping and waking cycles. In this particular surgery, however, the electrodes had gone astray and come to rest still at the midline, but at a somewhat more forward position in the brain, in a region called the septum.
The rat in question was placed in a large rectangular box with corners labeled A, B, C, and D and was allowed to explore freely. Whenever the rat went to corner A, Olds pressed a button that delivered a brief, mild electrical shock through the implanted electrodes. (Unlike the rest of the body, brain tissue does not have the receptors that allow for pain detection, so such shocks don’t produce a painful sensation within the skull.) After a few jolts, the rat kept returning to corner A and finally fell asleep in a different location. The next day, however, the rat seemed even more interested in corner A than the others. Olds and Milner were excited: They believed that they had found a brain region that, when stimulated, provoked general curiosity. However, further experiments on this same rat soon proved that not to be the case. By this time, the rat had acquired a habit of returning often to corner A to be stimulated. The researchers then tried to coax the rat away from corner A by administering a shock every time the rat made a step in the direction of corner B. This worked all too well—within five minutes, the rat relocated to corner B. Further investigation revealed that this rat could be directed to any location within the box with well-timed brain shocks—brief ones to guide the rat to the target location and then more sustained ones once it arrived there.
Many years earlier the psychologist B. F. Skinner had devised the operant conditioning chamber, or “Skinner box,” in which a lever press by an animal triggered either a reinforcing stimulus, such as delivery of food or water, or a punishing stimulus, such as a painful foot shock. Rats placed in a Skinner box will rapidly learn to press a lever for a food reward and to avoid pressing a lever that delivers the shock. Olds and Milner now modified the chamber so that a lever press would deliver direct brain stimulation through the implanted electrodes. What resulted was perhaps the most dramatic experiment in the history of behavioral neuroscience: Rats would press the lever as many as seven thousand times per hour to stimulate their brains. They weren’t stimulating a “curiosity center” at all—this was a pleasure center, a reward circuit, the activation of which was much more powerful than any natural stimulus. A series of subsequent experiments revealed that rats preferred pleasure circuit stimulation to food (even when they were hungry) and water (even when they were thirsty). Self-stimulating male rats would ignore a female in heat and would repeatedly cross foot-shock-delivering floor grids to reach the lever. Female rats would abandon their newborn nursing pups to continually press the lever. Some rats would self-stimulate as often as two thousand times per hour for twenty-four hours, to the exclusion of all other activities. They had to be unhooked from the apparatus to prevent death by self-starvation. Pressing that lever became their entire world (Figure 1.1).
Further work was done to systematically vary the placement of the electrode tips and thereby map the reward circuits of the brain. These experiments revealed that stimulation of the outer (and upper) surface of the brain, the neocortex, where sensory and motor processing mostly reside, produced no reward—the rats continued to press the lever at chance levels. However, deep in the brain, there was not just a single discrete location underlying reward. Rather, a group of interconnected structures, all located near the base of the brain and distributed along the midline, constituted the reward circuit. These included the ventral tegmental area, the nucleus accumbens, the medial forebrain bundle, and the septum, as well as portions of the thalamus and hypothalamus (more on these various regions later). Not all these areas were equally rewarding. Stimulation in some parts of this medial forebrain pleasure circuit could support self-stimulation rates of seven thousand lever presses per hour, while others elicited only two hundred per hour.
Figure 1.1 Self-stimulation of the pleasure circuit in a rat. When the rat presses the lever, it causes brief electrical stimulation to travel down the wire and activate the electrodes implanted deep in the rat’s brain, in various portions of the medial forebrain pleasure circuit. This setup can be modified in several useful ways. For example, the electronics can be configured so that a rat must make many lever presses to get a single stimulation. In addition, a hollow needle can be implanted together with the stimulating electrodes to inject drugs directly into the pleasure circuit. Illustration by Joan M. K. Tycko.
It’s hard to imagine now, but in 1953 the notion that motivational or pleasure/reward mechanisms could be localized to certain brain regions or circuits was highly controversial. The dominant theory, which had held sway for many years, was that excitation of the brain was always punishing and that learning and the development of behavior could be explained solely by punishment avoidance. This was called the drive-reduction hypothesis. In Olds’s characterization of the theory, “pain supplies the push and learning based on pain reduction supplies the direction.” There was no need for reward or pleasure: This model was all stick, no carrot. The pioneering experiments of Olds and Milner clearly demolished the punishment-only model in favor of a more comprehensive, hedonistic view that “behavior is pulled forward by pleasure as well as pushed forward by pain.”1
I know what you’re thinking: What does it feel like for a human to have his or her medial forebrain reward circuitry stimulated with an electrode? Does it produce a crazy pleasure that’s better than food or sex or sleep or even Seinfeld reruns? We do in fact know the answer to that question. The bad news is that that answer comes, in part, from some deeply unethical experiments.
Dr. Robert Galbraith Heath was the founder and chairman of the Department of Psychiatry and Neurology at Tulane University in New Orleans. He served from 1949 to 1980, and during that time the major focus of his work involved stimulation of the brains of institutionalized psychiatric patients, often African Americans, using surgically implanted electrodes. His main goal—to use brain stimulation to relieve the symptoms of psychiatric disorders such as major depression and schizophrenia—was laudable. However, he did not obtain proper informed consent from his patients and took decisions in experimental design that would never be approved by modern human-subjects ethical review boards.
Perhaps the most egregious example was reported in a paper entitled “Septal stimulation for the initiation of heterosexual behavior in a homosexual male,” published in the Journal of Behavioral Therapy and Experimental Psychiatry in 1972.2 The rationale behind this experiment was that because stimulation of the septal area evoked pleasure, if it was combined with heterosexual imagery it could “bring about heterosexual behavior in a fixed, overt homosexual male.” And so Patient B-19, a twenty-four-year-old male homosexual of average intelligence who suffered from depression and obsessive-compulsive tendencies, was wheeled into the operating room. Electrodes were implanted at nine different sites in deep regions of his brain, and three months were allowed to pass after the surgery to allow for healing (Figure 1.2). Initially stimulation was delivered to all nine electrodes in turn. However, only the electrode implanted in the septum produced pleasurable sensations. When Patient B-19 was finally allowed free access to the stimulator, he quickly began mashing the button like an eight-year-old playing Donkey Kong. According to the paper,
During these sessions, B-19 stimulated himself to a point that, both behaviorally and introspectively, he was experiencing an almost overwhelming euphoria and elation and had to be disconnected despite his vigorous protests.
So, not to put too fine a point on it, Heath’s patient responded just as Olds and Milner’s rats had. Given the chance, he would stimulate his pleasure circuit to the exclusion of all else.
Lest anyone think that it is only men—creatures of inherently base urges—who would respond in this manner, another recorded case, performed by a different group, involved a woman who received an electrode implant in her thalamus, an adjacent deep brain structure, to control chronic pain. This technique has proven effective for some patients whose severe pain is not well-controlled by drugs. However, in this patient the stimulation spread to nearby brain structures, producing an intense pleasurable and sexual feeling:
At its most frequent, the patient self-stimulated through out the day, neglecting her personal hygiene and family commitments. A chronic ulceration developed at the tip of the finger used to adjust the amplitude dial and she frequently tampered with the device in an effort to increase the stimulation amplitude. At times she implored her family to limit her access to the stimulator, each time demanding its return after a short hiatus.3
Figure 1.2 A patient of Dr. Robert Galbraith Heath with chronically implanted electrodes, one of which activated the medial forebrain bundle passing through the septum, a key part of the pleasure circuit. From Robert G. Heath, “Depth recording and stimulation studies in patients,” in Arthur Winter, ed., The Surgical Control of Behavior (Springfield, Il.: Charles C. Thomas, 1971), 24. Reprinted with permission from Charles C. Thomas.
Back to Patient B-19: Before his brain stimulation began, he was shown a “15 min long ‘stag’ film featuring sexual intercourse and related activities between a male and female.” Not surprisingly, he was sexually indifferent to this material and even a bit angry about being made to view it. Following pleasure circuit self-stimulation, however, he readily agreed to re-view the film “… and during its showing became sexually aroused, had an erection and masturbated to orgasm.” All this in the decidedly unsexy environment of the lab. So, with the patient starting to exhibit heterosexual tendencies, what were the experimenters to do? Would he ever have an actual sexual relationship with a woman? After careful consideration of all the options and with the well-being of the patient foremost in their minds, Drs. Heath and Charles E. Moan made a sober medical and scientific decision: Upon getting approval from the attorney general of the state of Louisiana, they hired a hooker to come to the lab at Tulane and attempt to seduce him. She succeeded—they had sexual intercourse. The concluding sentence to the lengthy, overly descriptive paragraph describing their two-hour-long sexual encounter reads, “Then, despite the milieu and the encumbrance of the electrode wires [poor B-19 was attached to an EEG machine the whole time], he successfully ejaculated [in her vagina].”
Did Patient B-19 actually become heterosexual? Following discharge from the hospital, he had a sexual relationship with a married woman for several months, much to the delight of Drs. Moan and Heath, who found this development quite encouraging. His homosexual activity was reduced during this period, but did not stop completely: He still liked to turn tricks with men to earn money. Long-term follow-up information was not available. Writing in the discussion section of their scientific report, Moan and Heath were enthusiastic about the prospects for this therapy: “Of central interest in the case of B-19 was the effectiveness of pleasurable stimulation of new and more adaptive sexual behavior.” While it’s clear that Patient B-19 found the brain stimulation to be intensely pleasurable, I’m not convinced that he truly became heterosexual, even temporarily. It should also be cautioned that this report concerns only a single individual, not a population (with a control group).
This study is morally repugnant on many different levels—the profound arrogance of attempting to “correct” someone’s sexual orientation, the medical risk of unjustified brain surgery, the gross violations of privacy and human dignity. Fortunately, homosexual conversion therapy with brain surgery and pleasure center stimulation was soon abandoned. Stepping back a bit, what we are left with, from this and a handful of other studies, is an appreciation of the immense power of direct electrical stimulation of the brain’s pleasure circuitry to influence human behavior, at least in the near term.
Let’s now take a minute to consider some important details of the pleasure circuit. I hesitate to burden you with neuroanatomy, but just a smidgen will go a long way in explaining how we experience pleasure. We’ll use the rat as an example, which is appropriate because the anatomy of the rat’s pleasure circuit is very similar to that of our own (Figure 1.3). When neurons in the region called the ventral tegmental area (VTA) are active, brief electrical impulses (called spikes) race from their cell bodies (located in the VTA proper) along long, thin information-sending fibers called axons. The axons have specialized structures at their endpoints called axon terminals. Some of the axon terminals of the VTA neurons are located some distance away in a region called the nucleus accumbens. When the traveling electrical spikes reach the axon terminals, they trigger the release of the neurotransmitter dopamine, which is stored in the terminals in tiny membrane-bound blobs called vesicles. When a spike enters the axon terminal, it initiates a complex series of electrical and chemical events that result in the fusion of the vesicle membrane with the membrane of the axon terminal, thereby causing the contents of the vesicle, including the dopamine neurons, to be released into a narrow fluid-filled space surrounding the axon terminal called the synaptic cleft. The dopamine molecules then diffuse and bind to specialized dopamine receptors on their target neurons, initiating a series of chemical signals therein (Figure 1.4).
Figure 1.3 The pleasure circuit in the brain of a rat. This view shows a section through the middle of the rat brain, oriented so that the nose is at the left and the tail at the right. The central axis of the pleasure circuit is the dopamine-containing neurons of the ventral tegmental area (VTA) and their axons, drawn in white, which project to the nucleus accumbens. These VTA neurons also send their dopamine-releasing axons to the prefrontal cortex, the dorsal striatum, the amygdala, and the hippocampus. The VTA neurons receive excitatory drive from the prefrontal cortex and inhibitory drive from the nucleus accumbens. Illustration by Joan M. K. Tycko.
Neurons of the VTA also send dopamine-releasing axons to other brain regions, including the amygdala and the anterior cingulate cortex, which are emotion centers; the dorsal striatum, involved in some forms of habit learning; the hippocampus, involved in memory for facts and events; and the prefrontal cortex, a region that controls judgment and planning (and that is particularly expanded in humans as compared with other mammals).
