Welcome to Your Brain (37 page)

also Chinese, also an immigrant, not far from his parents’ age. For these reasons, they like him. He

comes in, a bit harried. He is friendly, but he appears to have made his mind up about Sam’s mother.

Outside the office are many patients, some in other examination rooms, waiting for him.

Sam tries to persuade the doctor that his mother has had a stroke. The doctor is skeptical because

she also had some gradual memory decline before this event, a common sign of Alzheimer’s disease.

But this diagnosis doesn’t make sense; her recent memory loss is large and sudden. She has diabetes,

which is a risk factor for microstrokes and stroke in general. This could explain both the gradual and

sudden declines. Still he resists the idea, perhaps because stroke would often cause a sensory,

movement, or language problem in addition to the abrupt memory loss.

Together they look at the MRI scan report. It comes up mostly normal, but a phrase leaps out at

Sam: “anomalous low contrast focus in the anterior left thalamus, 4 mm wide.” This means that the

picture shows a little spot of dead tissue, a lesion, deep in her brain. This is it. This is the damage.

Her thalamus has been damaged by a tiny blood clot lodged in a blood vessel.

The doctor is not convinced. He says, “This lesion is so small, smaller than the nail of your little

finger.” He finished medical school nearly forty years ago. He might not even have taken a neurology

class. At some schools, it’s not required. The thalamus itself is less than an inch long. It transmits

information from one part of the brain to another, especially sensory information to the cerebral

cortex. But it also communicates with parts of the brain involved in memory. In the thalamus, four

millimeters is a big lesion. Eventually the doctor agrees to refer Sam’s mother to a neurologist.

Fifteen minutes later, he is off to his next patient.

Since her stroke, Sam’s mother has been having trouble learning about new facts and events. A

related form of memory is spatial navigation—the memory skill you use to get to your favorite

neighborhood coffee shop even before you’ve had the benefit of your morning coffee. These forms of

memory require structures located on the sides of the brain and in its core, in regions known as the

temporal lobe system (see
Chapter 23
).

The role of the thalamus in memory is relatively mysterious, partly because it’s composed of

many different nuclei (clusters of neurons). Some of these nuclei transmit sensory and motor

information. Others connect to assorted brain regions involved in other functions. We don’t know

what many of these nuclei do. In the laboratory, the way we find out is to damage a nucleus and see

what goes wrong, or to record electrical activity. We can also trace the wiring, the way that you might

trace a cable from the back of your stereo. In humans, it’s unethical to deliberately damage parts of

the temporal lobe or track the wiring inside the living brain. Therefore, stroke victims are a useful

source of information. Useful for the student of the brain, that is—unfortunate for the patient.

The thalamus, a small brain component, is a less-common place for strokes to occur than the

cortex, and a memory deficit after a thalamic stroke is unusual. This is partly because the thalamus is

a gateway to all parts of the cerebral cortex, and only certain of these pathways are involved directly

in memory.

With the specialist, Sam looks at a new set of MRI scans that reveal more detail than the ones

taken at the community hospital. In this scan, his mother’s brain shows two small spots, very close to

one another, in her anterior left thalamus. It looks as if a sharpshooter had aimed a BB gun at a target.

The doctor explains that the sharpness of these spots is strong evidence that a blood clot did indeed

lodge in her brain. A stroke of the other kind, caused by bleeding, probably would have resulted in

more widespread damage.

Sam’s mother had two big risk factors. First, her father had heart disease and may have died of a

stroke. This family history indicates that she may have inherited a predisposition to have a stroke.

Second, she has diabetes mellitus, a condition of high blood sugar, which she has not been treating

properly. For reasons that are not entirely known, untreated diabetes and high blood sugar increase

the risk of stroke. One possible reason is that diabetics have impaired blood flow, which can

increase the risk of clot formation.

Practical tip: Warning signs of stroke—and what to do

Detection:
How can you tell if you are having a stroke? If you experience a sudden

loss of feeling or movement in a particular part of your body, this may be a stroke or “brain

attack.” You may also experience a sudden inability to speak or recognize speech. If any of

these events occur, it is essential to get to an emergency room right away.

Treatment:
After a stroke occurs, immediate treatment, within three hours of the

stroke, can help reduce the damage. Only some large hospitals have the ability to diagnose

and treat stroke, so it’s a good idea to identify the right hospital in advance. The type of

treatment depends on whether the stroke is the more common kind, blockage of a blood

vessel (ischemic) or the less common kind, bleeding (hemorrhagic). For clotting strokes,

clot-busting drugs such as tissue plasminogen activator (tPA, also called Activase or

alteplase) can help. For hemorrhagic strokes, tPA would worsen the damage. In

hemorrhagic strokes, the treatment options are not as good, but can include drugs.

Prevention:
Lifestyle changes can help prevent stroke. Smoking and excessive alcohol

intake are major risk factors. Diets high in sugars and in saturated fats such as red meat and

eggs are associated with stroke. Conversely, green vegetables; some fish, such as salmon,

mackerel, and tuna; and the use of certain fats, such as canola, sunflower, or olive oil, in

cooking can all lower your risk. Finally, regular exercise reduces the chance of stroke.

Major predictors of stroke, especially in people over fifty-five, include excessive

weight, high blood pressure, and untreated diabetes. All of these predictors can be detected

by routine physical examinations. A history of previous stroke or transient ischemic attacks

is also an indicator of possible future stroke.

An additional way to prevent clotting strokes, the most common form, is the use of

antiplatelet medications. The most commonly available one is aspirin, which in small doses

reduces the risk of stroke and heart attack. Other antiplatelet drugs are also available that

attack clotting mechanisms more strongly. However, antiplatelet drugs are not appropriate

for some patients, including people with gastrointestinal bleeding.

To learn more about stroke, go to
http://www.strokecenter.org.

The specialist gives her some basic neurological tests. One is the three-object test. He gives her

three words—
blue, Paris, apple
—then changes the subject. Five minutes later, he asks for the three

words back. Nothing. However, she can do other things, like count backward by sevens: one hundred,

ninety-three, eighty-six … She can touch her nose with her eyes closed. Many functions are fine—but

not memory. She has also lost some memory of events before the stroke. She can’t remember the

terrorist attack of September 11, 2001—less than five months ago. Who could forget it? Now that’s

memory loss.

The doctor thinks her memory will improve somewhat over the next several years as her brain

rewires itself to get around the new damage. However, a full recovery is not likely. In the meantime,

there are new drugs that have some effect on memory loss, both in Alzheimer’s disease and in stroke-

induced memory loss. These drugs affect the neurotransmitter systems acetylcholine or glutamate. He

prescribes one.

Over the next few years, Sam’s mother’s function improved somewhat. She eventually learned to

pass the three-object test, so that the game of giving her three things to remember stopped fascinating

the family. She could remember things for many days, like when Sam was coming to visit next, or

what happened in the news the previous week. At the same time, her memory, which had once been

prodigious, was still severely impaired. She used to run a brisk business selling and developing real

estate, which required the continual recall of many facts, and going back to work remained

impossible for the rest of her life.

Chapter 30

A Long, Strange Trip: Drugs and Alcohol

William S. Burroughs was fascinated with altered states of experience. A lifelong drug user,

Burroughs wrote about his reactions to heroin, methadone, alcohol, cocaine, countless hallucinogens,

and other drugs in books like
Junky
,
Naked Lunch
, and
The Yage Letters
. Even so, Burroughs

experienced only a small fraction of the hundreds of mind-altering substances in the world. Most of

these drugs work by interfering with the actions of neurotransmitters. Some drugs mimic the action of

a naturally occurring transmitter; others enhance or block the action of transmitters. You may recall

from
Chapter 3
that some receptors respond to their transmitters by generating electrical signals that

affect the likelihood that the neuron will fire a spike. Another type, called metabotropic receptors,

generates chemical signals that affect the internal workings of the cell. Metabotropic receptors are

frequent targets of mind-altering drugs. Their job is to modulate the functions of neurons or whole

networks, often in subtle ways, making them essential in governing mood and personality.

The stars of this world are the monoamine neurotransmitters, which regulate mood, attention,

sleep, and movement. The monoamines include dopamine, serotonin, adrenaline, and nor-adrenaline.

These busy molecules are important in Parkinson’s disease, Huntington’s disease, depression, bipolar

disorder, schizophrenia, headache, and sleep disorders.

Many mind-altering drugs interact with serotonin, which regulates sleep and mood. Serotonin

interacts with more than a dozen receptors, each of which is found in a different subset of cells.

Squirts of serotonin over here can make a neuron spike faster, over there make it more sensitive.

Because there are so many receptors for serotonin, it is possible to play with them in subtle and

interesting ways.

Did you know? Ecstasy and Prozac

Ecstasy and Prozac have very different uses: the first is a club drug, and the second is a

treatment for depression. Surprisingly, both drugs have the same effect on the same

molecular target. After serotonin is released, it is removed from the synapse by a

transporter protein that sucks it into nearby neurons. Both Ecstasy and Prozac block the

action of this transporter.

MDMA (methylenedioxymethamphetamine), better known as Ecstasy, was first

synthesized in 1912. In the 1960s, MDMA was introduced in psychotherapy because it

induces intense feelings of well-being, friendliness, and love for other people. For similar

reasons, it became popular at nightclubs several decades later.

MDMA prunes back serotonin-secreting nerve terminals for a period lasting up to

several months, though without killing the neurons. It may have some risk for addiction

relating to its amphetamine-like structure, but the abuse potential is mitigated because the

emotional effects of the drug diminish with repeated use. (Contrary to a myth, MDMA use

does not deplete spinal fluid. This tale started from a study in the 1980s, in which MDMA

users volunteered to give spinal fluid for analysis, and the rumor mill distorted the findings

almost beyond recognition.) Ecstasy’s effects begin soon after it is taken and last for many

hours.

Prozac, on the other hand, requires repeated use over many weeks to take effect. Like

Zoloft and Paxil, Prozac is a specific serotonin reuptake inhibitor, one of the most

commonly prescribed types of drug. Although we know what these drugs do at a molecular

level, exactly how they affect mood is not known. One possibility is that brain

neurochemistry may adapt to the repeated administration of these drugs, for instance by

making less serotonin to compensate for the extra serotonin hanging around at synapses.

An unresolved question is why a single dose of Prozac does not lead to Ecstasy-like

effects. One possibility is that these drugs enter the brain at different rates. If Prozac enters

the brain more slowly than Ecstasy, it might not give the same initial rush. Another

possibility is that Ecstasy, which is structurally similar to amphetamine, can also block

dopamine uptake, leading to effects similar to those of cocaine and amphetamine.

Many hallucinogenic drugs are naturally occurring chemicals, such as those found in magic

mushrooms and peyote, but the most precisely acting hallucinogen is the synthetic chemical lysergic

acid diethylamide (LSD). LSD, or acid, is not addictive and causes no lasting organic damage to the

brain. It binds very tightly to particular serotonin receptors, so doses of LSD are extremely small,

typically between twenty-five and fifty micrograms—one ten-thousandth the weight of an aspirin