The Undiscovered Mind: How the Human Brain Defies Replication, Medication, and Explanation

Book by Horgan John

Chapter One: Neuroscience's Explanatory Gap

By 1979 Freudian psychology was treated as only an interesting historical note. The fashionable new frontier was the clinical study of the central nervous system....Today the new savants probe and probe and slice and slice and project their slides and regard Freud's mental constructs, his "libidos," "Oedipal complexes," and the rest, as quaint quackeries of yore, along the lines of Mesmer's "animal magnetism."

-- Tom Wolfe, In Our Time

In Phaedo Plato described the last hours of Socrates, who had been imprisoned and sentenced to death by Athenian authorities. Socrates told friends who had assembled in the prison why he had accepted his death sentence rather than fleeing. At one point, Socrates ridiculed the notion that his behavior could be explained in physical terms. Someone who held such a belief, Socrates speculated, would claim that

as the bones are lifted at their joints by the contraction or relaxation of the muscles, I am able to bend my limbs, and that is why I am sitting here in a curved posture...and he would have a similar explanation of my talking to you, which he would attribute to sound, and air, and hearing...forgetting to mention the true cause, which is, that the Athenians have thought fit to condemn me, and accordingly I have thought it better and more right to remain here and undergo my sentence.

This is the oldest allusion I know of to what some modern philosophers call the explanatory gap. The term was coined by Joseph Levine, a philosopher at North Carolina State University. In "Materialism and Qualia: The Explanatory Gap," published in Pacific Philosophical Quarterly in 1983, Levine addressed the puzzling inability of physiological theories to account for psychological phenomena. Levine's main focus was on consciousness, or "qualia," our subjective sensations of the world. But the explanatory gap could also refer to mental functions such as perception, memory, reasoning, and emotion -- and to human behavior.

The field that seems most likely to close the explanatory gap is neuroscience, the study of the brain. When Plato wrote Phaedo, no one even knew that the brain is the seat of mental functioning. (Aristotle's observation that chickens often continue running after being decapitated led him to rule out the brain as the body's control center.) Today neuroscientists are probing the links between the brain and the mind with an ever more potent array of tools. They can watch the entire brain in action with positron emission tomography and magnetic resonance imaging. They can monitor the minute electrical impulses passing between individual nerve cells with microelectrodes. They can trace the effects of specific genes and neurotransmitters on the brain's functioning. Investigators hope that eventually neuroscience will do for mind-science what molecular biology did for evolutionary biology, placing it on a firm empirical foundation that leads to powerful new insights and applications.

Neuroscience is certainly a growth industry. Membership in the Society for Neuroscience, based in Washington, D.C., soared from 500 in 1970, the year it was founded, to over 25,000 in 1998. Neuroscience journals have proliferated, as has coverage of the topic in premier general-interest journals such as Science and Nature. When Nature launched a new periodical, Nature Neuroscience, in 1998, it proclaimed that neuroscience "is one of the most vigorous and fast growing areas of biology. Not only is understanding the brain one of the great scientific challenges of our time, it also has profound implications for society, ranging from the basis of memory to the causes of Alzheimer's disease to the origins of emotions, personality and even consciousness itself." Neuroscience is clearly advancing; it is getting somewhere. But where?

I once asked Gerald Fischbach, the head of Harvard's Department of Neuroscience and a former president of the Society for Neuroscience, to name what he considered to be the most important accomplishment of his field. He smiled at the naiveté of the question. Neuroscience is a vast enterprise, he pointed out, which ranges from studies of molecules that facilitate neural transmission to magnetic resonance imaging of whole-brain activity. It is impossible, Fischbach added, to single out any particular finding, or even a set of findings, emerging from neuroscience. The field's most striking characteristic is its production of such an enormous and still-growing number of discoveries. Researchers keep finding new types of brain cells, or neurons; neurotransmitters, the chemicals by which neurons communicate with each other; neural receptors, the lumps of protein on the surface of neurons into which neurotransmitters fit; and neurotrophic factors, chemicals that guide the growth of the brain from the embryonic stage into adulthood.

Not long ago, Fischbach elaborated, researchers believed there was only one receptor for the neurotransmitter acetylcholine, which controls muscle functioning; now at least ten different receptors have been identified. Experiments have turned up at least fifteen receptors for the so-called GABA (gamma-amino butyric acid) neurotransmitter, which inhibits neural activity. Research into neurotrophic factors is also "exploding," Fischbach said. Researchers had learned that neurotrophic factors continue to shape the brain not only in utero and during infancy but throughout our life span. Unfortunately, neuroscientists had not determined how to fit all these findings into a coherent framework. "We're not close to having a unified view of human mental life," Fischbach said.

Fischbach was spotlighting one of his field's most paradoxical features. Although reductionist is often used as a derogatory term, science is reductionist by definition. As the philosopher Daniel Dennett once put it, "Leaving something out is not a feature of failed explanations, but of successful explanations." Science at its best isolates a common element underlying many seemingly disparate phenomena. Newton discovered that the tendency of objects to fall to the ground, the swelling and ebbing of seas, and the motion of the moon and planets through space could all be explained by a single force, gravity. Modern physicists have demonstrated that all matter consists basically of two types of particles, quarks and electrons. Darwin showed that all the diverse species on earth were created through a single process, evolution. In the last half-century, Francis Crick, James Watson, and other molecular biologists revealed that all organisms share essentially the same DNA-based method of transmitting genetic information to their offspring. Neuroscientists, in contrast, have yet to achieve their reductionist epiphany. Instead of finding a great unifying insight, they just keep uncovering more and more complexity. Neuroscience's progress is really a kind of anti-progress. As researchers learn more about the brain, it becomes increasingly difficult to imagine how all the disparate data can be organized into a cohesive, coherent whole.

The Humpty Dumpty Dilemma

In 1990, the Society for Neuroscience persuaded the U.S. Congress to designate the 1990s the Decade of the Brain. The goal of the proclamation was both to celebrate the achievements of neuroscience and to support efforts to understand mental disorders such as schizophrenia and manic depression (also known as bipolar illness). One neuroscientist who opposed the idea was Torsten Wiesel, who won a Nobel prize in 1981 and went on to become president of Rockefeller University in New York. (He stepped down to return to research at the end of 1998.) Born and raised in Sweden, Wiesel is a soft-spoken, reticent man, but when I interviewed him at Rockefeller University in early 1998, he became heated at the mention of the "Decade of the Brain."

The idea was "foolish," he grumbled. "We need at least a century, maybe even a millennium," to comprehend the brain. "We still don't understand how C. elegans works," he continued, referring to a tiny worm that serves as a laboratory for molecular and cellular biologists. Scientists had discovered some "simple mechanisms" in the brain, but they still did not really understand how the brain develops in the womb and beyond, how the brain ages, how memory works. "We are at the very early stage of brain science." (Nevertheless, in 1998 behavioral scientists -- a broad category including psychologists, geneticists, anthropologists, and others -- began lobbying for the decade beginning in the year 2000 to be named the Decade of Behavior.)

Wiesel himself participated in one of neuroscience's paradigmatic discoveries. Like many other scientific triumphs, this one resulted from both hard work and serendipity. In 1958 Wiesel and another young neuroscientist, David Hubel, were conducting experiments on the visual cortex of a cat in a "small, dingy, windowless basement lab" (according to one account) at the Johns Hopkins Medical School. After implanting an electrode in the cat's visual cortex, they projected images on the cat's retina with a slide projector attached to an ophthalmoscope. They presented the cat with two simple stimuli: a bright spot on a dark background and a dark spot on a bright background. When the electrode detected an electric discharge from a neuron, a device similar to a Geiger counter would emit a loud click.

Wiesel and Hubel were getting inconclusive results when one of their slides became stuck in the projector. After unjamming the slide, they slowly pushed it into its slot. Suddenly the electrode monitor started firing like "a machine gun." Wiesel and Hubel eventually realized that the neuron was responding to the edge of the slide moving across the cat's field of vision. In subsequent experiments, they found neurons that respond to lines only at specific orientations relative to the position of the retina. As the investigators moved the electrode through the visual cortex, the orientation of the lines to which the neurons responded kept changing, like a minute hand circling a clock. In 1981 Wiesel and Hubel received a Nobel prize for their research.

These findings are emblematic of a larger trend in neuroscience. Arguably the most important discovery to emerge from the field is that different regions of the brain are specialized for carrying out different functions. This insight is hardly new; Franz Gall said as much two centuries ago when he invented phrenology (which degenerated into a pseudoscientific method for determining character from the shape of the skull). But modern researchers keep slicing the brain into smaller and smaller pieces, with no end to the process in sight.

As recently as the 1950s, many scientists believed that memory is a single -- albeit highly versatile -- function. The researcher Karl Lashley was a prominent advocate of this view. He argued that memories are processed and stored not in any single location but throughout the brain. As evidence, he pointed to experiments in which lesions in the brains of rats did not significantly affect their ability to remember how to navigate mazes. What Lashley failed to realize was that rats have many redundant methods for navigating a maze; if the rat's ability to recollect visual cues is damaged, it may rely instead on olfactory or tactile cues.

Subsequent experiments involving both humans and other animals revealed many types of memory, each underpinned by its own region of the brain. The two major categories of memory are explicit, or declarative, memory, which involves conscious recollection; and implicit, or nonconscious, memory, which remains below the level of awareness but nonetheless affects behavior and mental functioning.

Memory has been divided into other categories as well, some of which overlap. Short-term memory, which is sometimes called working memory, allows us to glance at a telephone number and recall it just long enough to dial it a few seconds later. Long-term memory keeps that same telephone number in permanent storage, ready to be accessed when needed. Procedural memory lets us acquire and perform such reflexive skills as driving a car, touch-typing, or playing tennis. Episodic memory enables us to recall specific events.

Experiments have also identified a phenomenon known as priming, which is similar to the old notion of subliminal influence. Subjects are exposed to a stimulus, such as a sound or image, so briefly that they never become consciously aware of it and cannot recall it later. Yet tests show that the stimulus has been imprinted on the brain at some level. In one set of experiments, subjects are shown a list of words too briefly for it to be stored in short-term memory. Later the subjects are asked to play a game similar to the television game Wheel of Fortune. Given the clue "o-t-p-s," they must guess what the full word is. Subjects who have previously been exposed to a list of words containing octopus are much more likely to guess correctly, even though they cannot explicitly recall whether the list included octopus.

Technologies such as positron emission tomography (PET) and magnetic resonance imaging (MRI) have accelerated the fragmentation of the brain and mind. PET scans monitor short-lived radioactive isotopes of oxygen that have been injected into the blood. High levels of the isotope indicate increased blood flow and thus increased neural activity. MRI dispenses with the need for an injection of a radioactive substance. A powerful electromagnetic pulse causes certain atoms to align in a particular direction, like iron filings arranged around a magnet. When the magnetic field is relaxed, the atoms emit radiation at characteristic frequencies.

Imaging studies often focus on subjects performing some task: solving mathematical puzzles, sorting images according to category, memorizing lists of words. Those regions of the brain that are most active are assumed to be crucial to the activity. Karl Friston, an MRI specialist at the Institute of Neurology in London, compared this cataloguing of neural "hot spots" to Darwin's patient gathering of data on animals from around the world. "Without this catalogue of functional specialization," Friston said, "I don't think that one's going to go far in assembling a useful and accountable theory of brain organization."

But Friston felt that the push toward localization had gone too far. Too many studies simply associate a given region with a given function "without any reference to any conceptual framework or proper or deep understanding of the functional architecture of the brain." Different parts of the brain are also clearly interconnected, and understanding these neural connections is crucial to understanding the mind. "Looking at the correlations between different areas," Friston said, "has been very much underemphasized."

Rodolfo Llinas, a neuroscientist at New York University, was even more critical of the manner in which neuroimaging is being used, particularly in psychiatry. "You find somebody who has a particular problem, and you see a red spot on the front of the cortex and you say, 'Okay, so that spot of the cortex is the site where you have bad thoughts.' It's absolutely incredible! The brain does not function as a single-area organ!" Llinas compared these studies to phrenology, the eighteenth-century pseudoscience that divided the brain into discrete chunks dedicated to specific functions. "You have a patient, and you put the patient into the instrument, and you write a paper, because you can just see it," Llinas said. "It's phrenology!"

Llinas recalled that neuroscience previously went through ...