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Authors: Omar Manejwala

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Beyond Neurotransmitters

The
Real
Brain Science of Craving and Decision-Making

Alcoholism: Disease
or
of Choice

Medical science news is very difficult to interpret. One study shows that drinking a little wine is good for you, while another suggests it’s very bad. One study shows that hormone replacement therapy for women is a good idea, while another suggests it can lead to breast cancer. One week the news is eat more of this food, and the next week it’s eat less. In the midst of this flood of conflicting information, it’s easy to either get an oversimplified (and inaccurate) picture of the science of health and wellness or draw the conclusion that we don’t really know anything at all. The reality is that we know quite a bit about the brain and its function, and much of it
is
easily understood; what’s missing is basic education about the way the brain works and how its processes affect experiences and decisions.

Most people have heard of neurotransmitters, the chemicals that brain cells use to communicate with each other. Today’s news is filled with conflicting information about these chemicals and how we can modify them: exercise increases serotonin, serotonin is responsible for good mood, too much serotonin leads to irritability, too little leads to depression. Television ads for antidepressants might convince you that all you need is a little more of a certain chemical and you’ll be okay, as if your brain contained two beakers, one for serotonin and one for norepinephrine, and all you need is to fill up one of the beakers if you are running a little low. Doctors may reinforce this simplistic idea by describing depression as a
chemical imbalance.
“Don’t worry, Mr. Jones. You just need some more serotonin because you are running a little low.”

In order to understand why you crave and how you make decisions, you need a more sophisticated understanding of the brain and its function. Although estimates vary, most scientists agree that the typical human brain contains about 100 billion nerve cells, or neurons, and at least that many supporting cells, called glia. Your neurons have cell bodies and projections called axons and dendrites. It is often helpful to think of axons as broadcast antennae and dendrites are receiving antennae. The gaps between axons and dendrites are called synapses. When an electrical impulse is activated along an axon, a neurotransmitter is released into that gap. The neurotransmitter then activates the dendrite of the next neuron (often by attaching to a special protein called a receptor) and
voilà,
one neuron just “talked” to another one! (See the illustration below.) Each individual neuron can have many synapses. Thus, your brain is highly networked, and small changes in one area can produce dramatic effects throughout the brain.

Your brain has gray matter and white matter. The gray matter of your brain consists mostly of the cell bodies of your neurons and the dendrites. The white matter is white because the long axons (transmitting antennae) are covered with a whitish fat-and-protein insulation called myelin. Myelin helps the electrical signal travel more efficiently along the axon. Your cerebral cortex is the outer part of your brain and is mostly gray matter. Deeper in your brain are nuclei, dense regions of cell bodies. These deeper regions, surrounded by white matter, are also gray matter and are responsible for key functions of your brain. For example, one set of nuclei deep in your brain is called the thalamus. Your thalamus functions as a sort of relay system, as sensory and motor signals pass through it and are processed. In fact, all sensations except smell are processed in the thalamus. Nerve cells related to smell go directly to the cortex without the relay. Some scientists believe that smell has a powerful impact on decision-making because of this fact, and in my experience working with addicts, smells often seem to trigger the worst cravings.

How Your Brain Lies to You

One important function of the brain is to give you accurate information about your surroundings so you can function in the world. Another important brain function is to lie to you. Several medical conditions provide dramatic examples of this. For example, patients with schizophrenia and other psychotic conditions may experience auditory or visual hallucinations. Olfactory hallucinations (where you smell something that isn’t there) are common with certain seizure disorders and tumors. People with the psychiatric condition called Capgras syndrome believe that those around them have been replaced by imposters. In de Clérambault’s syndrome, you believe that someone is in love with you even though they are not. In delusional parasitosis, you become convinced that you are infested with parasites when you are not. When people have these disorders, no amount of evidence or argument can convince them that they are wrong. In later chapters, you will learn how your brain actually lies to you all the time, even without the presence of mental or physical illness.

My father, who is a cardiologist originally from India, recounted a story to me about a small village where a woman believed she had a frog in her womb. No amount of rationalizing with her worked, and she went from doctor to doctor requesting a treatment. Finally, one physician put her under anesthesia, made a superficial incision in her lower abdomen, then woke her up and showed her a live frog that he had secretly sent his nurse to procure from a local stream, proclaiming she was cured. Everyone thought this was a brilliant solution, and the woman was so grateful to have been cured—that is, until the woman returned to the surgeon two weeks later pointing out that “the frog had babies” and that another surgery was needed. You can’t talk someone out of their delusion.

Brain injuries can provide even more dramatic examples of how your brain can lie to you. In some forms of severe epilepsy, the treatment involves severing part of one of the bridges between your left and right brain, called the corpus callosum. When people have this surgery, they can develop split-brain syndrome—the two halves of their brain no longer work together. For example, they are unable to verbally name things that their right brain is observing because their speech center is on the left side of their brain. They will often make up bizarre explanations for this phenomenon (called confabulation, which also occurs with a certain form of alcoholic brain damage called Korsakoff’s syndrome). Some strokes can result in a condition called hemineglect, where a person doesn’t believe that half of their body belongs to them. These people, when asked to draw a clock face, might only draw half of the clock (the numbers 1–6, for example). Such a person might not be able to move his left arm, which he also is “neglecting.” In severe cases, when you pick up his left arm and show it to him and ask him what it is, he might respond “a piece of meat.”

Decision-Making and Your Brain

The link between certain regions of your brain and your ability to make sound decisions can indeed be very dramatic. In November 1848, a physician named John Harlow published a case report in the
Boston and Medical Surgical Journal
titled “Passage of an Iron Rod through the Head” about a man named Phineas Gage. Phineas was a twenty-five-year-old married railroad worker in Vermont. On September 13, 1848, Phineas was compacting explosive powder into a boulder using an iron tamping rod that was 3 feet, 7 inches long, 1 ¼ inches in diameter, and pointed at one end. Phineas was looking away, toward some of his coworkers, when the powder accidentally sparked, and the resulting explosion propelled the rod into his left cheekbone, through the floor of his left eye socket, and out the midline of his skull, landing some thirty feet away.

Phineas was a well-loved guy, and his coworkers immediately ran to his aid. Within minutes he was speaking and was rushed in an oxcart to a local hotel where, with just a little assistance, he climbed a flight of stairs and changed his clothes, all the while with a gaping hole clear through the left frontal lobe of his brain. A mere ninety minutes after the accident, he was examined by Dr. Harlow and found to be doing remarkably well. Over the next few days he was up and about, with no difficulties in speech, motor activity, or sensory abilities. At that point, Harlow was quite amazed that Phineas didn’t seem to have anything major wrong with him, even though he had lost a substantial chunk of his brain! The doctor was no doubt wondering: What exactly is the purpose of that part of the brain if you can lose it without any consequences?

Phineas’s wife, however, knew better, as she observed that he was never quite the same. Over the next few weeks, months, and years, it became clear that what had changed about Phineas were his choices and his personality. The changes were so dramatic that, twenty years later, Harlow was compelled to publish a follow-up report in the
Bulletin of the Massachusetts Medical Society
detailing the tremendous changes in Phineas resulting from the loss of his orbitofrontal cortex. In Harlow’s words:

His contractors, who regarded him as the most efficient and capable foreman in their employ previous to his injury, considered the change in his mind so marked that they could not give him his place again. He is fitful, irreverent, indulging at times in the grossest profanity (which was not previously his custom), manifesting but little deference for his fellows, impatient of restraint of advice when it conflicts with his desires, at times pertinaciously obstinate, yet capricious and vacillating, devising many plans of future operation, which are no sooner arranged than they are abandoned in turn for others appearing more feasible. In this regard, his mind was radically changed, so decidedly that his friends and acquaintances said he was “no longer Gage.”
1

In other words, Phineas was rude, impulsive, lazy, impatient, and stubborn. He was no longer the man he used to be and could not relate to his coworkers, friends, and family like he once did. Phineas Gage’s behavior sounds a lot like how someone might describe an addict. Physicians had known for many years that injuries to the brain could result in problems with movement, speech, sensation, and consciousness. But Phineas’s case was the first to show that judgment was also localized to a particular region of the brain. Put another way, when Phineas lost a critical part of his brain, what he wanted and what he chose changed. His friends were absolutely correct: he was “no longer Gage.”

When I was a resident physician at Duke, I began a research project examining auditory hallucinations in schizophrenics with a brilliant mentor, Dr. Lawrence Dunn. Our interest was in rapid transcranial magnetic stimulation (rTMS), a technique where a powerful electromagnetic coil that can activate regions of the brain beneath the coil is applied to the scalp. The device was still experimental at that time, and we ordered one from a British company. It sat in U.S. customs for months while we waited for the Food and Drug Administration (FDA) to figure out what it was and approve our paperwork. (Nowadays these devices are common and are used to treat a range of conditions, especially depression.) There is nothing particularly special about the workings of this device. It’s simply a copper wire coil wrapped a few thousand times inside a handheld wand with an electrical current running through it. You could probably buy the supplies at Radio Shack and build your own, although I wouldn’t recommend it! As any junior scientist knows, an alternating current produces a moving magnetic field that will induce a current in any nearby conductive material. And the axons of neurons are conductive material. So the mere act of holding the rTMS device over a person’s head and turning it on actually activates the nerve cells.

As I learned more about this technique (and as I waited for the device to arrive), I became less interested in auditory hallucinations and more fascinated with the research of a neuroscientist named Alvaro Pascual-Leone. Pascual-Leone had published an amazing study that garnered little attention in the media, despite its groundbreaking findings.
2
He asked his subjects to extend their right or left index finger every time they heard a click. It was the subjects’ choice whether they wanted to extend their left or their right index finger. He then placed the coil over specific positions on each subject’s scalp and carried out the experiment. What he noticed was that the placement of the coil seemed to influence which finger the subjects selected—he was influencing their decisions by magnetically inducing currents in their brains. Holding a device over their heads changed the way they made choices! But even more important, the people whose decisions had been influenced by the coil’s placement
had no idea whatsoever that their choices had been affected by the coil.
They just thought they were picking at random.

Once again, as in the case of Phineas Gage, changes in the brain affected choices and desires without the affected people even realizing they were being influenced! Several years later, in 2007, Pascual-Leone and his team were also able to use the rTMS technique to reduce risk-taking behavior in subjects, something that is extremely important when dealing with cravings and addiction.
3

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