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Today we have technologies that the phrenologists could only fantasize about. MRI gives us precise measurements of the sizes of cortical regions, eliminating the silly method of feeling head bumps. And by scanning the brains of many humans, researchers can collect enough data to go beyond anecdotes like Witelson's study of Einstein's brain. What have the neo-phrenologists found?

They have demonstrated that IQ is correlated
with the sizes of the frontal and parietal lobes. The correlation has turned out to be slightly stronger than that between IQ and overall brain size, in keeping with the idea that these lobes are more critical to intelligence. (The occipital and temporal lobes are mainly devoted to sensory abilities like vision and hearing.) Still, the correlation is disappointingly weak.

But these studies don't fully follow the spirit of phrenology, which not only divided the brain into regions but also divided the mind into separate abilities. We all know people who are superb at mathematics but less skilled verbally, and vice versa. Today many researchers reject the notion of IQ and general intelligence as simplistic. They prefer to speak of “multiple intelligences,” and these turn out to be correlated with the sizes of specific brain regions. London taxi drivers
have an enlarged right posterior hippocampus, which is a region of the cortex thought to be involved in navigation. In musicians,
the cerebellum is larger and certain cortical regions are thicker. (The enlargement of the cerebellum makes sense, as it is thought to be important for fine motor skills.) Bilinguals
have a thicker cortex in the lower part of the left parietal lobe.

While these findings are fascinating, they are only statistical. If you read the fine print, you'll see that the brain regions are only larger
on average.
It remains the case that the sizes of brain regions are almost useless for predicting the abilities of an individual.

 

Differences in intellectual ability can cause difficulties, but they're usually not catastrophic. Other kinds of mental variation, however, exact terrible suffering and are hugely costly to our society. In industrialized countries, an estimated six of every hundred people have a severe mental disorder,
and almost half suffer a milder disorder at some point in their lives. Most disorders respond only partially to behavioral and drug therapies, and many have no known treatment at all. Why is it so difficult to fight mental disorders?

The discoverer of a disease is usually the first to describe its symptoms. In 1530 the Italian physician Girolamo Fracastoro utilized the unusual medium of an epic poem,
Syphilis sive morbus Gallicus
(“Syphilis or the French Disease”). He named the disease in honor of the first man to contract it, the mythical shepherd Syphilus, who was punished with sickness by the god Apollo. In three books of Latin hexameter, Fracastoro described the symptoms of syphilis, recognized that it was sexually transmitted, and prescribed some remedies.

Syphilis causes ugly skin lesions and awful physical deformities. Later on, another horrible symptom can emerge: insanity. In his 1887 horror story “Le Horla,” the French writer Guy de Maupassant imagined a supernatural being who torments the narrator, first by physical sickness and then by madness: “I am lost! Somebody possesses my soul and governs it! Somebody orders all my acts, all my movements, all my thoughts. I am no longer anything in myself, nothing except an enslaved and terrified spectator of all the things which I do.” The narrator finally resolves to end his suffering by killing himself. The story seems semi-autobiographical, as Maupassant suffered from syphilis contracted in his twenties. In 1892 he attempted suicide by cutting his throat. Committed to an asylum, Maupassant died the next year at the age of forty-two.

The painter Paul Gauguin and the poet Charles Baudelaire may also have suffered from syphilis. We have no proof, however, because a disease cannot be reliably diagnosed based on symptoms alone. Two people with the same disease may have different symptoms, and two people with different diseases may have similar symptoms. To diagnose and treat a disease, we'd like to know its cause rather than its symptoms. The bacterial cause of syphilis was discovered in 1905, and the first drugs that killed the bacteria soon followed. These drugs were effective in the early stages of syphilis, but they could not eradicate the disease after it invaded the nervous system. In 1927 the German physician Julius Wagner-Jauregg won the Nobel Prize for his bizarre cure for neurosyphilis. In addition to administering drugs, he deliberately infected patients with malaria. The resulting fever somehow killed off the syphilis bacteria, at which point he introduced drugs that cured the malaria. After World War II, Wagner-Jauregg's cure was replaced by penicillin and the other antibacterial drugs known as antibiotics. Syphilis is no longer a major cause of brain disease.

Diseases caused by infection are relatively easy to cure, because we know the cause. But what about other kinds? Alzheimer's disease (AD), which commonly strikes the elderly, starts with memory loss and progresses to dementia, a generalized deterioration of mental abilities. In the late stages, the brain shrinks, leaving empty space inside the skull. Were they alive today, the phrenologists would explain AD as being caused by a decrease in brain size, but this explanation would be unsatisfactory. Shrinkage of the brain occurs long after memory loss and other symptoms first appear, and furthermore, shrinkage is itself more a symptom than a cause. It happens because brain tissue dies, but what causes that?

Searching for clues, scientists examined autopsy tissue from AD patients and discovered microscopic “junk” called plaques and tangles littering the brains. In general, an abnormality in the cells of the brain associated with a disease is known as a
neuropathology.
Plaques and tangles appear in the brain well before the death of cells, and closer to the onset of AD symptoms. These neuropathologies are currently regarded as the defining characteristic of AD, as the symptoms of memory loss and dementia can also occur in other diseases. Scientists have not yet figured out what causes plaques and tangles to accumulate, but they hope that reducing these neuropathologies might cure AD.

The most puzzling mental disorders come with no clear and consistent neuropathology. Here we are really stumped. These disorders, still defined only by their psychological symptoms, are the furthest from being cured. They may involve anxiety, as in panic and obsessive-compulsive disorders, or mood, as in depression and bipolar disorder. Two of the most debilitating are schizophrenia and autism.

The symptoms of autism
are most memorably conveyed by clinical description:

 

David was 3 when he was diagnosed as autistic. At that time he hardly looked at people, was not talking, and seemed lost in his own world. He loved to bounce on a trampoline for hours and was extremely adept at doing jigsaw puzzles. At 10 years of age David had developed well physically, but emotionally remained very immature. He had a beautiful face with delicate features. . . . He was and still is extremely stubborn in his likes and dislikes. . . . More often than not his mother has to give in to his urgent and repeated demands, which easily escalate into tantrums.

David learned to talk when he was 5. He now goes to a special school for autistic children, where he is happy. He has a daily routine, which he never varies. . . . Some things he learns with great skill and speed. For example, he learned to read all by himself. He now reads fluently, but he doesn't understand what he reads. He also loves to do sums. However, he has been extremely slow to learn other skills, for example, eating at the family table, or getting dressed. . . .

David is now 12 years old. He still does not spontaneously play with other children. He has obvious difficulties in communicating with other people who don't know him well. . . . He makes no concessions to their wishes or interests and cannot take onboard another person's point of view. In this way David is indifferent to the social world and continues to live in a world of his own.

 

This case study includes all three of the symptoms that define autism: social impairment, difficulties with language, and repetitive or rigid behaviors. The symptoms appear before three years of age and often lessen later on, but most autistic adults are unable to function
without some sort of supervision. No known treatment is very effective, and there is certainly no cure.

Speaking more poetically, Uta Frith has described autism as a “beautiful child
imprisoned in a glass shell.” Many other types of disabled children may have heart-wrenchingly obvious physical deformities. That's not the case for the autistic, who look superficially fine or even beautiful. Their appearance deceives parents, who have difficulty believing that something is fundamentally wrong. They hope in vain to break through the “glass shell”—the social isolation of autism—and liberate a normal child. But the healthy guise of the autistic child hides a brain that is not normal.

The best-documented abnormality is one of size. When the American psychiatrist Leo Kanner originally defined the syndrome
in a landmark 1943 paper, he noted in passing that five children out of his eleven case studies had large heads.
Over the years, researchers have studied many more autistic children and found that their heads and brains
are indeed enlarged on average—especially the frontal lobe,
which contains many areas involved in social and linguistic behaviors.

Does that mean brain size is a good predictor of autism? If it were, we could be confident that the phrenological approach is on the right track toward explaining autism. But we should be careful not to commit a common statistical fallacy concerning rare categories. Consider a very special type of person, professional football players. They are markedly larger than the average person. Can we turn this around and predict that anyone much larger than average is likely to be a professional football player? This prediction rule would work well with what's called a balanced population—one containing equal numbers of football players and regular people. If you sorted them by size, you'd be pretty accurate. But if you looked instead at the general population and predicted that any large person drawn from it was a football player, you'd be wrong most of the time. These people would just be tall, muscular, or obese for other reasons. Similarly, predicting that all children with big brains are autistic would be highly unreliable. There is much more to playing in the NFL than being large, and much more to being autistic than having a big brain.

The media often report studies claiming accurate prediction of rare mental disorders based on some property of the brain. These studies usually turn out to be less impressive than they sound, because the accuracy is only for a balanced population, not for the general population. If, however, you really know a disease's cause, it should serve as an unerring diagnostic, even for the general population. That's the case for many infectious diseases, which can be detected through blood tests for microbes.

 

Schizophrenia is as perplexing as autism. It typically begins in the twenties, with the striking and sudden onset of hallucinations (most commonly hearing voices), delusions (often of persecution), and disorganized thinking. Here is a vivid first-person account
of such symptoms, collectively known as psychosis:

 

Though I cannot remember how it was initiated, at one point while I was sitting on the toilet, a quick rush of adrenaline gripped me. My heart was racing. Voices started coming out of nowhere, and I thought that I was mentally tuned into a television program being broadcast worldwide in which rock stars and scientists were overthrowing the world governments (through the means of computers, biology, psychology, and voodoo-type ritual). Right then and there!

At that moment the people communicating on TV were announcing all of their intentions and motives for a new world order. I seemed to be at center stage of the discussion with a number of rock stars and scientists who were hiding elsewhere throughout the world.

 

Psychosis can terrify the victim, as well as alarm and distress others. It's the most obvious sign of schizophrenia, but it also accompanies other mental disorders. So an accurate diagnosis of schizophrenia requires additional symptoms, such as lack of motivation, flattened emotion, and diminished speech. These are the “negative” symptoms of schizophrenia, in contrast to the “positive” or psychotic symptoms. (Here, “positive” and “negative” are not value judgments; they refer to the presence of disordered thought and the relative absence of emotion, respectively.) Schizophrenia is treated with drugs that eliminate psychosis. The drugs are not a complete cure, however, because they are less effective for the negative symptoms.
Most schizophrenics remain unable to live independently.

As with autism, the best-documented abnormality of the schizophrenic brain has to do with size. MRI studies have shown that overall brain volume
is reduced on average by just a few percentage points. The percent reduction of the hippocampus is slightly greater but still not very large. Researchers have also imaged the ventricular system, a set of fluid-filled caverns and passages in the brain. The lateral and third ventricles
are enlarged on average by 20 percent. Since the ventricles are hollow spaces in the brain, their enlargement might be related to the observed reduction in brain volume. While it's encouraging that some sort of difference has been found, this correlation is as weak as the statistical findings reported for autism. Diagnosing schizophrenia for an individual using brain size, hippocampal size, or ventricular volume would be wildly inaccurate.

To make progress in treating autism and schizophrenia, it would help to find clear and consistent neuropathologies like the plaques and tangles of Alzheimer's disease, but no similar accumulation of “junk,” or other signs of dying or degenerating cells, is consistently associated with autistic or schizophrenic brains. Neo-phrenology suggests that something is abnormal about the brain, but we have failed to find it. In 1972 the neurologist Fred Plum wrote despairingly that “schizophrenia is the graveyard
of neuropathologists.” Researchers have discovered some clues since then, but there has been no dramatic breakthrough.