Biological Bases of Mind and Behavior

In the 19th century, William James (1842-1910) defined psychology as the science of mental life, attempting to understand the cognitive, emotional, and
motivational processes that underlie human experience, thought, and action. But even in the earliest days of scientific psychology, there was a lively debate about how to go about studying the mind. Accordingly, there arose the first of several "schools" of psychology, structuralism and functionalism.

Structuralism and Functionalism

One point of view, known as structuralism tried to study mind in the abstract. argued that complex mental states were assembled from elementary sensations, images, and feelings. Structuralists used a technique known as introspection (literally, "looking into" one's own mind) to determine, for example, the elements of the experience of a particular color or taste. The major proponents of structuralism were:

Structuralism was beset by a number of problems, especially the unreliability and other limitations of introspection, but the structuralists did contribute to our understanding of the basic qualities of sensory experience (see Boring's The Physical Basis of Consciousness, 1927).

Another point of view, known as functionalism, was skeptical of the structuralist claim that we can understand mind in the abstract. Based on Charles Darwin's (1809-1882) theory of evolution, which argued that biological forms are adapted to their use, the functionalists focused instead on what the mind does, and how it works. While the structuralists emphasized the analysis of complex mental contents into their constituent elements, the functionalists were more interested in mental operations and their behavioral consequences. Prominent functionalists were:

Psychological functionalism is often called "Chicago functionalism", because its intellectual base was at the University of Chicago, where both Dewey and Angell were on the faculty (functionalism also prevailed at Columbia University). It is to be distinguished from the functionalist theories of mind associated with some modern approaches to artificial intelligence (e.g., the work of Daniel Dennett, a philosopher at Tufts University), which describe mental processes in terms of the logical and computational functions that relate sensory inputs to behavioral outputs.

The functionalist point of view can be summarized as follows:

In these lectures, we pick up this last point, by examining the biological foundations of our mental lives in the brain and the rest of the nervous system.

For an interactive tour of the brain and behavior, see "The Brain from Top to Bottom", a website developed by Bruno Dubuc of McGill University and the Canadian Institute of Neurosciences, Mental Health, and Addiction.

Organization of the Nervous System

Like all biological entities, the nervous system is organized hierarchically, with larger units composed of smaller units. 

The nervous system is one such system, allowing various organs and tissues to communicate with, and influence, each other. This communication is accomplished by means of electrical discharges.

Other bodily systems include the:

Whereas the traditional systems of the body all consist of tissues and organs, the immune system, consisting of Toll-like receptors, B cells, and T cells, is found at the cell level.

Hierarchical Level	Examples in the Nervous System
Cells	Neurons Afferent Efferent Interneurons
Tissues	Nerves Afferent Efferent Nuclei and Ganglia
Organs	Brain Brainstem Spinal Cord
Systems	Nervous System(s) consisting of the nerves, spinal cord, and brain Peripheral vs. Central Autonomic vs. Somatic Sympathetic vs. Parasympathetic Spinal vs. Cranial Cortical vs. Subcortical
Organism	The living, thinking, behaving person composed of several overlapping and interconnecting systems, including the nervous system.

For an online tour of the human body, created through CAT and MRI scans, go to the Visible Human Project of the National Library of Medicine: www.nlm.nih.gov/research/visible.

The hierarchical organization of biological structures continues above the level of the individual organism:

Neurons

At the lowest level of biological organization, the cell, we have the neuron, which comes in three basic types:

Note: If you want to reduce confusion between "afferent" and "efferent", think of "affect" as a "feeling", and of something having an "effect" on something else.

The human brain contains about 86-100 billion neurons -- most, interestingly, in a structure known as the cerebellum, rather than the cerebral cortex itself.  The upper estimate is the conventional one; the lower estimate comes from Suzana Herculano-Houzel, a Brazillian neuroscientist who developed a new method of counting. 

Structure of the Neuron

No matter what its type, every neuron consists of a cell body, with its nucleus, a number of dendrites stemming out from the cell body, and a long axon, ending in a number of terminal fibers.

The axon may be covered with a myelin sheath, and this sheath may be interrupted by breaks, called the Nodes of Ranvier.

An individual neuron may be drawn schematically as follows:

Each of these elements has a particular function:

In this way, neural impulses are carried from one point to another in the nervous system.

A sequence of these three types of neurons constitutes the reflex arc -- described by Charles Sherrington (Oxford University), a British physiologist who won the Nobel Prize for Physiology or Medicine in 1932 (shared with Edgar D. Adrian of Cambridge). Essentially, the reflex arc processes sensory inputs and generates motor outputs. Although things are actually more complicated than this, conceptually, at least, the reflex arc is the basic building block of behavior.  It goes back at least as far as the 17th-century French philosopher Rene Descartes, who coined the term reflex.  In Descartes's view, energy from a stimulus is picked up by various sensors and transmitted to the brain, where it is reflected "back" in the form of a motor response.

Glia Cells

In addition to neurons, glia cells (also known as neuroglia) also comprise another elementary unit in the nervous system. There are roughly a trillion glia cells in the human brain.  That's about 10 times the high estimate of the number of neurons, which might be the source of the common assertion that we use only about 10% of our brains.  But this is a complete misunderstanding.  All of our neurons are actively engaged in mental activity.

Glial cells aid neural functioning in several ways:

Although it was once thought that the glia cells are not directly involved in mental processes, recent evidence suggests that, in addition to the support functions outlined above, glia may form an information-processing and communication network of their own, running parallel to the neurons (see "The Other Half of the Brain" by R. Douglas Fields, Scientific American, 04/2004). For example, UCB's Prof. Marian Diamond, famous for her undergraduate neuroanatomy course, discovered that while there was nothing remarkable about Einstein's brain so far as neurons were concerned, certain parts of the cerebral cortex had a remarkably high concentration of glia cells.Diamond interpreted this as reflecting a greater metabolic activity in his neurons.  Later research showed that Einstein's corpus callosum was bigger than average, possibly allowing for greater connectivity between his left and right hemispheres (Einstein was a famously visual thinker); there were also some anatomical differences: for example, his frontal lobes had four gyri, not the usual three.

For the saga of Einstein's brain, which is an even better tale than the saga of Descartes' head, see "Genius in a Jar" by Brian D. Burrell, Scientific American, 9/2015.  Also Finding Einstein’s Brain (2018) by Frederick E. Lepore.

Even if they do not play a direct role in mental processes, glia cells do appear to be implicated in certain forms of brain disease.

The Synapse

Other neural structures are built up from neurons, but neurons themselves are not physically connected; instead, they are separated by a gap, called the synapse -- a term coined by the physiologist Charles Sherrington. The synapse separates the terminal fibers of one neuron (the presynaptic neuron) from the dendrites and cell body of the next (the postsynaptic neuron). Each neuron contains a large number of terminal fibers and dendrites: thus, each neuron synapses onto a large number (1,000 or so, on average) of other neurons, producing a rich network of interconnections. Given that the adult human brain contains about 100 billion neurons, each making approximately 1,000 synaptic connections with other neurons, there are roughly 100 trillion synapses -- more synapses in a single brain than there are stars in our Milky Way galaxy).

Several neurons, each separated by a synapses from each of the others, may be drawn schematically as follows.

The neuron may be thought of as a wire that conducts an electrical charge from the cell body down the axon to the terminal fibers. The electrical discharge of a neuron is based on an electrochemical process.

At this point the action potential meets the synapse, and the problem is for the action potential to get across the synaptic gap, from the presynaptic neuron to the postsynaptic neuron. (Here's where the "wire" analogy breaks down, because individual neurons aren't connected to each other, the way electrical wires are.)

The precise mechanism by which the neural impulse propagates down the axon from the cell body to the synapse is too complicated to detail here: you'll learn all about this if you take a more advanced course in biological psychology or neuroscience. Put briefly, it's not exactly like an electrical current. Rather, the impulse travels by means of a series of depolarizations involving the exchange of sodium and potassium ions. This process is described by the Hodgkin-Huxley model, described by Alan Hodgkin and Andrew Huxley  in a classic 1952 paper (Andrew Huxley is a descendant of T.H. Huxley, known as "Darwin's bulldog" for his vigorous defense of evolutionary theory in the 19th century; he's also related to Aldous Huxley, who wrote Brave New World as well as the Doors of Perception, a report of his experiences with psychedelic drugs that gave The Doors their name). For their discovery, Hodgkin and Huxley shared the 1962 Nobel Prize in Physiology or Medicine with John Eccles.

Eccles, for his part, won the Prize for discovering the mechanism of synaptic transmission. Traditionally, neurophysiologists believed that synaptic transmission occurred electrically, by something like a spark. Eccles demonstrated that the mechanism was actually chemical in nature. He and his colleague Bernard Katz also identified the first neurotransmitter, acetylcholine. Katz, for his part, got his own Nobel Prize in 1970, for his "kiss and run" model of synaptic activity -- which really is too complicated for a course at this level!

But for the record, two other physiologists, Otto Loewi (Graz University, Austria) and Henry Dale (Cambridge), had already received the Prize for earlier work on acetylcholine in the nervous system.

Neurotransmitters

This feat is accomplished by means of synaptic transmission. The arrival of a neural impulse at the terminal fiber of the presynaptic neuron induces the discharge of a chemical known as a neurotransmitter substance. Neurotransmitter flows into the synapse, and is taken up by the dendrites (technically, the dendritic spines) of the postsynaptic neuron. If a sufficient quantity is taken up, the postsynaptic neuron is depolarized. Another substance clears used neurotransmitter out of the synaptic cleft, permitting the cycle to start all over again. In this way, neural impulses travel from the peripheral sensory receptors to the spinal cord, up the spinal cord to the brain, from one brain structure to another, back down the spinal cord from the brain, and out from the spinal cord to the muscles and glands.

Strictly speaking, the presynaptic and postsynaptic neurons are not completely separated. Specialized cell-adhesion molecules form a physical connection between them, thus stabilizing their connection. But the neural impulse isn't transmitted by these physical connections. The neural impulse passes from one neuron to another chemically, by means of synaptic transmission.

Neurotransmitters are differentiated according to function. Excitatory neurotransmitters depolarize a postsynaptic neuron, while inhibitory neurotransmitters hyperpolarize it, making it more difficult to discharge. Some neurotransmitters have both excitatory and inhibitory effects, depending on the presence of other transmitters. There are also excitatory and inhibitory synapses -- presumably because they release excitatory and inhibitory neurotransmitters; but the point is that there's a difference between the synapse and the neurotransmitter.

So glutamate and GABA are the primary neurotransmitters, operating throughout the nervous system.  There are many more neurotransmitters, however, which perform specialized functions.

Acetylcholine (ACh), another prominent "excitatory" neurotransmitter, provides a good example of the ways in which synaptic transmission works. ACh has an inhibitory effect on the vagus nerve, which serves the heart; and an excitatory effect on the nerves that serve the voluntary musculature, including the muscles that supply the lungs. Consider the following toxic effects on the function of excitatory ACh:

Biological sleep aids (sometimes called hypnotics, although they have nothing to do with hypnosis) provide another, perhaps less threatening, example.

In any case, the result is the cessation of neural transmission in the nerves supplying the skeletal musculature, including the lungs. The person cannot breathe, and will die of suffocation unless he or she is artificially respirated until the toxin is metabolized and washes out of the system. Thus, skeletal paralysis, and death, is the final common pathway uniting the three toxic effects.

Technically, the terms excitatory and inhibitory apply to the receptors on the postsynaptic neuron, rather than to the neurotransmitters themselves -- which is why some neurotransmitters can have both excitatory and inhibitory functions. But, at our level, it is convenient to think of the neurotransmitters themselves as being excitatory, or inhibitory, or both.

In the lock-and-key model of neurotransmitter function, each neurotransmitter has a particular molecular structure, or shape, which can fits only certain receptor molecules. The neurotransmitter is like a key, and the receptor is like a lock. Only if the neurotransmitter fits into a particular receptor can it excite or inhibit the postsynaptic neuron. Some drugs used in the treatment of schizophrenia work by binding themselves to certain receptors, taking the place of certain neurotransmitters, and thus effectively jamming the lock in the lock-and-key system, and preventing the neurotransmitter from functioning properly. So-called designer drugs are deliberately structured to take the place of particular neurotransmitters.

There are many different kinds of neurotransmitters, each with a particular chemical structure and range of action. You don't have to memorize all these neurotransmitters -- this is a course in psychology, not molecular and cellular neuroscience! But there are some whose names will crop up from time to time, and you should recognize them as familiar.

Some of these neurotransmitters are involved in various neurological and psychiatric syndromes.

Dynamics of the Neural Impulse

Returning to normal neural functioning, the neural discharge conforms to the all-or-none law formulated by Edgar D. Adrian (1889-1977) -- work for which he won the Nobel Prize in Physiology or Medicine for 1932 (shared with Charles Sherrington, another neurophysiologist). According to the all-or-none law, either a neuron fires or it does not, and if it fires it does so in a single burst of activity. Each neuron has a certain threshold for discharge -- a certain amount of stimulation that is necessary for depolarization to occur.

After firing, the neuron enters a refractory period, during which it must recover before it can discharge again.

One way in which stimulation crosses threshold, obviously, is from a single super-threshold stimulus from a single presynaptic neuron. This action releases enough neurotransmitter to depolarize the postsynaptic neuron. In many cases, however, such presynaptic stimulation is subthreshold. If so, the all-or-none law comes into effect: the postsynaptic neuron doesn't discharge "just a little bit"; rather, the neural impulse simply travels no further.

However, subthreshold stimulation can depolarize the postsynaptic neuron by virtue of summation. That is, under some circumstances presynaptic activity can accumulate. If the aggregate presynaptic stimulation crosses the threshold, the postsynaptic neuron will fire. If not, again transmission stops.

There are two kinds of summation.

Temporal and spatial summation are extremely important. Consider one implication of the all-or-none law. If stimulation is super-threshold, the neuron fires, no matter how far above threshold the stimulation is. If stimulation is subthreshold, the neuron does no matter how close to the threshold it is. In order words, the firing of individual neurons cannot record the intensity of stimulation. But, obviously, we are able to distinguish between different intensities of stimulation: lights are bright or dim, sounds are loud or soft, tastes and smells are strong or weak. Note, however, that while increasing stimulation has no effect on the magnitude of the impulse of any single neuron, it does have two other effects. (1) Increasing intensity increases the rate at which single neurons fire. (2) Increasing intensity increases the involvement of adjacent neurons. Thus, the nervous system as a whole records intensity in terms of both the rate at which individual neurons discharge, and the number of individual neurons that are discharging simultaneously.

Nerves, Ganglia, and Nuclei

At the tissue level, the nervous system is comprised of nerves, ganglia, and nuclei.

The nerves come in two forms, the type of neurons they're composed of.

The ganglia and nuclei are composed of interneurons. The distinction between these two types of tissues is based on location.

Ganglia and nuclei serve as the central nervous system in so-called "primitive" organisms, but are also found in the nervous systems of more complex organisms.

Hierarchical Organization of the Nervous System

The nervous system itself is also hierarchically organized, depending on the particular tissues and organs involved. We distinguish first between the central nervous system (CNS), composed of the brain, the spinal cord, and the brainstem that joins them, and the peripheral nervous system (PNS), consisting of all the nerves leading to and from the CNS.

The Peripheral Nervous System

There are two branches of the PNS:

The Autonomic Nervous System

The ANS, in turn, also contains two branches, the sympathetic nervous system (SNS again, just to create confusion with the somatic nervous system), and the parasympathetic nervous system (PNS).

The sympathetic nervous system mobilizes the body to meet emergencies.  In this so-called flight or fight response (so named by Walter B. Cannon), the secretion of the hormone adrenalin (epinephrine) leads to emotional arousal, while the secretion of noradrenalin (norepinephrine) releases stored sugar into the bloodstream, providing more energy to the muscles. At the same time, blood is re-channeled from the surface of the body to the muscles: this promotes physical activity (sugar gets to the muscles faster), and lessens bleeding in the case of an injury.

Actually, "flight or fight" is something of a misnomer, because the initial response of many organisms to a stressor is to freeze in place.  So, "flight or fight" should really be "freeze, flight, or fight".  But the shortened version, "flight or fight" has become commonplace, so we'll stick with it.  However, in a moment we'll see that even the fuller formulation isn't quite right.

The parasympathetic nervous system normally mediates vegetative functions such as digestion, elimination, and reproduction.

There are important differences in function between the sympathetic and parasympathetic branches of the autonomic nervous system.

Prolonged exposure to stress leads to what Hans Selye has called the general adaptation syndrome, which consists of three stages:

Sex Differences in Stress Response? The classic view of the autonomic nervous system, which we owe to Walter B. Cannon, is that it mediates "flight or fight" responses of the organism to stressful events. More recently, Shelly Taylor and her associates at UCLA discovered that almost all of this research was based on the responses of male organisms. The female of the species, Taylor et al. argue, typically responds with a different pattern of behavior, which they have labeled "tend and befriend": that is, under stress females either protect their young or provide support to others. Of course, there are individual differences within each sex: these labels apply to group trends only. Apparently, the "choice" between these reaction patterns is influenced by the organism's hormonal endowment (e.g., the presence of the male hormone testosterone or the female hormone estrogen).

The details of an organism's stress response may differ in other ways as well, depending on the nature of the stress and the organism's appraisal of it. For an overview of the stress response, see M.E. Kemeny, "The Psychobiology of Stress", in Current Directions in Psychological Science, 2003, 12(4), 124-129.

The Somatic (or Skeletal) Nervous System

The somatic nervous system (the other SNS) is further divided into two main branches, the spinal and cranial nerves.

The 12 Cranial nerves connect to the brain and brainstem. As a rule, cranial nerves are highly specialized:

By contrast, the 31 spinal nerves (mostly arranged in pairs, extending to the left and right side of the body), all combine sensory and motor functions: the afferent branch of each nerve, composed of afferent neurons, meets the spinal cord at its dorsal root, at the back of the body (think of a shark's dorsal fin), while the efferent branch, composed of efferent neurons, connects at the ventral root, along the front.

The distribution of spinal nerves has two interesting properties:

The Central Nervous System

The CNS consists of the spinal cord, brainstem, and brain.

Spinal Cord

The spinal cord conducts neural impulses between the periphery of the body and the brain and brainstem. Several different tracts, or bundles of nerves, run within the spinal cord:

A break in the spinal cord causes a neurological syndrome known as paraplegia, which entails a loss of conscious sensation and voluntary movement in body sites served by spinal nerves that connect to the spinal cord below the site of the cut. A break in the middle or lower portion of the spinal cord may result in a loss of sensory and motor functions only in the lower part of the body, including the legs and feet. If the break is very high, impairing the upper portion (including the arms and hands) as well as the lower part, the condition is called quadriplegia.

Even when the break is very high in the spinal cord, a cranial nerve, the vagus nerve, maintains vital functions such as heart rate and respiration.

Despite the break in the spinal cord, not all functions are lost: many spinal reflexes remain intact, because they are mediated solely at the level of the spinal cord, and do not require the involvement of higher nervous centers in the brain.

Such spinal reflexes include the patellar reflex (the jerking movement of your leg when your doctor taps your knee), and scratching at the site of an irritation, as well as penile erection, ejaculation, urination, and defecation.All these behaviors can occur, as involuntary, reflexive response to appropriate stimulation, in paraplegic individuals.

The spinal reflexes remain intact because all the necessary interneurons needed to mediate the stimulus-response connection are contained in the spinal cord itself -- in the gray matter, to be exact. But, in the case of paraplegia, they do have some special properties:

The Brainstem

The brainstem is the portion of the central nervous system that is situated between the spinal cord and the brain. Hard to differentiate precisely from the brain itself, it contains primitive structures often assigned to the hindbrain and the midbrain, as described below. There is also a forebrain. These divisions are so named because, in most animals, the spinal cord runs horizontally. Thus, the hindbrain is toward the back of the animal, and the forebrain towards the front. However, humans walk upright. Thus, the hindbrain is at the bottom, closest to the spinal cord, while the forebrain is at the top, furthest away.

The hindbrain, comprising the lower portion of the brain stem, consists of:

Separate from the brain stem, but also part of the hindbrain, is the cerebellum (from the Latin for "little cerebrum", because that's what it looks like -- similar shape, lots of folds). A major function of the cerebellum is to integrate sensory and motor data to help the organism maintain a sense of balance and exercise fine motor control. Cerebellar functioning can be impaired by alcohol, leading to loss of balance (in acute intoxication) or tremors (as a chronic effect). Although the cerebellum is the "little" cerebrum, in fact it contains many more neurons than the cerebral cortex -- by one popular estimate, about three times more.

The cerebellum has traditionally been construed as a "primitive" neural structure, recent research has revealed that it can be involved in a host of fairly complex mental functions, including the timing of both sensory signals and motor movements. The cerebellum is actively involved in the classical conditioning of motor responses, as in eyeblink conditioning. Other theorists suggest that the cerebellum provides support functions for the rest of the brain, including monitoring sensory data and maximizing the quality of sensory input -- particularly with respect to tactile exploration of the environment (see "Rethinking the 'Lesser brain'" by J.M. Bower and L.M. Parsons, Scientific American, 08/03).  As we acquire a motor skill, such as grasping an object or playing a musical instrument, control of motor activity gradually shifts from the cerebral cortex to the cerebellum -- a process that will be described further in the lectures on Learning, to follow.

The midbrain, comprising the middle portion of the brainstem, includes the reticular formation (from the Latin word reticulum, meaning "net").The reticular formation also is important in regulating cortical arousal. Cats who have suffered surgical destruction of the reticular formation lapse into a constant state of sleep, and can be awakened only by loud noises or other intense stimulation, if at all. Cats whose reticular formation is continually stimulated by implanted microelectrodes remain constantly awake; when the current is turned off, they return to their regular sleep-wake cycle.

The (Fore)Brain

The forebrain can be further divided into two parts:

These subcortical structures are sometimes referred to as the diencephalon.

The Cerebral Cortex

The cerebral cortex looks like one big mass of tissue, but it is also possible to differentiate among various major parts by locating three major orientation points which, together, form a map of cerebral cortex.

Note that the lobes can also be identified in a medial (interior) view of the brain.

The map of the cerebral cortex shows two different views of the brain: the lateral view simply looks at the brain from the side. The medial view looks at the brain from the midline, or the longitudinal fissure; this view is, essentially "from the inside out". If two structures are named, the medial structure is closer to the midline, the lateral one is further away.

Some other terms commonly used in neuroanatomy are:

Within each of these lobes, further "territories" are demarcated by the folds which mark their surface. These come in two types: the outward folds are called gyri (plural for gyrus), while the inward folds are called sulci (plural for sulcus). These folds are necessary because, despite appearances, the cerebral cortex isn't a big spongy glob of neurons, but rather a thin sheet of neural tissue that has to be folded and crumpled in order to fit inside the skull -- much as a large piece of cloth must be wadded up so it can fit inside a small bowl. Actually, it's like two thin sheets of tissue, one for each hemisphere, each about 12 inches in diameter. Despite their thinness, each sheet consists of about six distinct layers of neurons.

Why the brain folds precisely the way it does is a mystery. It's not a random process, because some folds are the same in all brains, and even have names -- like the inferior or third frontal gyrus (F₃) and the superior or first temporal gyrus (T₁), which lie on opposite sides of the lateral (Sylvian) fissure. Other folds differ from brain to brain. According to one theory, the cerebral cortex folds the way it does because of mechanical stresses and strains on individual axons produced as the cortex grows inside the brain case.  In any event, the pattern of folds is pretty much established at the time of birth.  It is possible that the precise pattern of folding differs in individuals with such major mental illnesses as schizophrenia and autism.

For more on the development of gyri and sulci, see "Sculpting the Brain" by Claus C. Hilgetag and Helen Barbas, Scientific American, 02/2009..

Anatomical studies reveal even more fine-grained subdivisions of cerebral cortex, within each lobe and subcortical structure. For example, Korbinian Brodmann (1909) described the cytoarchitectonics (from the Greek cyto, meaning "cell", and architekton, meaning "organized structure") of the brain, distinguishing 50 areas, mostly demarcated by gyri and sulci, but more importantly differentiated according to cell structure or organization. These Brodmann areas are analogous to separate tissues or organs within major portions of the brain, invisible to the naked eye. Furthermore, these different structures in the nervous system, sometimes marked by gyri or sulci, are linked by specific neural pathways to form brain circuits or brain systems -- a concept originally formulated by the American neuroscientist Roger Sperry, who shared the Nobel Prize in Physiology or Medicine in 1981. These pathways permit structures within the circuit/system to communicate with each other.

Brodmann's map is still in use, but it has its limitations.  For one thing, Brodmann identified only 43 areas, while current research has identified at least 180.  Moreover, Brodmann's map shows only the left hemisphere, and only the surface of the cortex, leaving subcortical areas unmapped.  To correct for these deficiencies, a group of German neuroscientists led by Katrin Amunts employed up-to-date histological techniques and digital imaging to produce a new cytoarchitectonic map, including both hemispheres and both cortical and subcortical regions (Amunts et al., Science, 08/21/2020).  The resulting Julich-Brain Atlas (named after the research center where the work was done) is a 3D image of the entire brain, with the different areas marked out in color.  It is a remarkable technical achievement, and a thing of genuine beauty. 

Cortical Development

The cerebral cortex (forebrain) is also called neocortex, because it was the last organ in the nervous system to develop. This is true whether you view development phylogenetically (from the Greek word phylon, meaning "tribe" or "race"), in terms of the evolution of species, or ontogenetically (from the Greek word onto-, meaning "existence" or "being"), in terms of the development of the individual species member. This is particularly true for the prefrontal cortex, the "foremost" part of the forebrain.

If you look at the brains of many different species, from snake to cat to human, the brain gets larger, but so of course does the animal. The important observation as that in the most recently evolved species, such as mammals and especially primates, a greater proportion of CNS tissue is devoted to cerebral cortex -- and especially the prefrontal cortex responsible for executive functions. Expansion of prefrontal cortex is also characteristic of hominid evolution, as in the comparison of "Neanderthal" and "Cro-Magnon" man.

Here's another, more recent comparison, by the McGill University Institute of Neuroscience, which makes the same point (thanks to Kelly Lowman for finding it).

This is the standard story, found in almost all neuroscience textbooks: the human brain, and in particular the cerebral cortex and the cerebellum, and especially the prefrontal cortex, is much larger than would be expected given our body size.  For example, gorillas generally exceed humans with respect to body size, but their brains are only about 1/3 the size of ours.  It is sometimes added that the human brain is also special in terms of the amount of white matter, or in terms of certain types of neurons (such as "von Economo neurons, named for the researcher who first described them, and thought to be important for social cognition).  But the basic story is summarized by the encephalization quotient, or EQ -- roughly, the ratio of brain size to size of the head.  In the chimpanzee, our closest living primate relative, EQ = about 3.  In humans, EQ = about 7.5.  No other animal comes even close.  If you plot brain size as a function of body (or just head) size, humans are outliers.  This high EQ is, traditionally, held to be the key to human intelligence.

On the other hand, a new approach to comparative neuroanatomy pioneered by Suzana Herculano-Houzel's method suggests a more nuanced account of brain evolution. 

• As noted earlier, she counted about 86 million neurons in the human brain.  That's fewer than the number usually given, which is 100 million. 
  
• She also found that we have fewer glial cells than we thought.  It's often asserted that we have about 10 times as many glia as neurons, but in fact the ratio of neurons to glia appears to be closer to 1:1.
  

This, H.-H. suggests, is the true key to the evolution of the brain.  For most mammalian species, brain evolution involved expansion of the cerebral cortex.  At some point, however, primates branched from other mammals, who continued to follow the standard neuronal density rules, and began packing more neurons into less brainspace.

(For details, see "The Human Brain in Numbers: A Linearly Scaled-Up Primate Brain" by Suzana Herculano-Houzel, Frontiers in Human Neuroscience, 2009; "Brain scaling in mammalian evolution as a consequence of concerted and mosaic changes in numbers of neurons and average neuronal cell size" by Herculano-Houzel et al., Frontiers in Human Neuroscience, 2014; The Human Advantage: A New Understanding of How Our Brain Became Remarkable by Herculano-Houzel, 2016; a nicely readable summary of her research appears in "The Remarkable (But Not Extraordinary) Human Brain", by Herculano-Houzel, Scientific American Mind, 03-04/2017.) 

Another traditional view undermined by recent neuroanatomical studies concerns "birdbrains", an epithet usually directed toward a stupid or scatterbrained person.  In fact, many birds are quite smart, and even creative, in terms of their problem-solving abilities.  As we'll see later, in the lectures on Learning, pigeons were used in the classic studies of instrumental (operant) conditioning by B.F. Skinner and his associates.  And crows and other corvid species (like ravens) have been observed inventing tools and engaging in other forms of complex cognition.  For a long time, it was thought that the cognitive abilities of birds were limited by the fact that their brains had no cerebral cortex, but it turns out that this isn't exactly true.  Birds have a cortex-like forebrain structure known as a pallium, which is densely packed with neurons.  And while it was long thought that the pallium in the bird brain lacked the layering characteristic of mammalian cortex, it has recently been discovered that the pallium of the bird brain also has a layered structure (Stacho et al., Science 09/25/2020).  Humans and other mammals have a pallium too, but because it was thought to be uniquely layered, the mammalian pallium was given a special designation -- namely, cerebral cortex.  It is generally a rule that the more neurons there are in the pallium (cortex), the greater the cognitive capacity of the species.  Bird-neurons are very small, which enables them to be so densely packed into the bird-pallium.  Which, at a neurobiological level of explanation, accounts for the excellent learning and problem-solving abilities of pigeons, crows, and other avian species. 

Similarly, it is no surprise that as the fetus and child matures, the brain gets larger. What is interesting is that the relative size of the cerebral cortex gets larger, compared to other CNS structures. As the brain matures, more folds appear as more cortical tissue has to fit into the skull.

Development of the brain continues after birth, at least through adolescence, perhaps until as late as the mid-20s (see "Crime, Culpability, and the Adolescent Brain" by Mary Beckman, 07/30/04, from which the graphic is taken). A longitudinal MRI study by Natin Gogtay and his associates (2004) shows a spurt of growth in gray matter immediately prior to puberty, following by a progressive replacement of gray matter by white matter -- perhaps a reflection of progressive myelinization of the brain, which we know continues after birth. The density of interconnections among brain areas also increase during adolescence. Development also proceeds from back to front, with the frontal lobes of the brain being the last to mature. Because the frontal lobes are associated with executive control functions, this immaturity of frontal-lobe structures in the brains of adolescents and young adults has been linked to problems in impulse control. Some neuroscientists and legal scholars have gone so far as to suggest that, because of such brain immaturity, adolescents and even young adults should not be held entirely culpable for criminal acts and other elements of misbehavior. The US Supreme Court, which has already decided that mentally retarded individuals are less culpable for their crimes by virtue of their diminished intellectual capacity (in the Atkins case, 2002), will address this issue of diminished responsibility for "normal" adolescents in the Simmons case (2004). As Beckman puts it, the Supreme Court may well decide that, in some respects, adolescence is "akin to mental retardation".

From Structure to Function

The brain is an amazing structure: it's been called the most complex entity in the universe.

That's pretty amazing, but we're doing more than anatomy here. We really want to know how these organs, tissues, systems, and circuits are related to mind and behavior. In other words, what are the psychological functions of these different brain structures?

According to the general principle known as localization of function, or functional specialization, different parts of the brain serve different psychological functions. This idea originated with Franz Joseph Gall (1788-1828), Johann Spurzheim (1776-1832), George Combe, and others who promoted a pseudoscience known as phrenology. Phrenology was popularized in America by Nelson Sizer and Orson Squire Fowler (and his bother Lorenzo), and you can sometimes purchase a ceramic copy of Fowler's "phrenological head" in novelty stores. Well into the 19th century, the brain was thought to be a single, massive, undifferentiated organ. But according to Gall and his followers, the brain is composed of discrete organs, each associated with some psychological faculty, such as morality or love. In classic phrenological doctrine, there were about 35-40 such faculties, and the entire set of faculties comprises a common-sense description of human abilities and traits.

Gall and other phrenologists inferred the associations between these abilities and traits and brain locations by looking at exemplary cases: if, for example, an obese person had a bulge in some part of his skull, the area of the brain underneath must control eating. The famous case of Phineas Gage, a railway-construction foreman who in 1848 sustained severe damage "in the neighborhood of Benevolence and the front part of Veneration" when a tamping iron was driven through his left eye socket and out the top of his head (and lived to tell about it), was a linchpin of arguments about phrenology in particular and functional specialization in general. (Interestingly, Gage is actually an ancestor of Fred Gage, a Salk Institute neuroscientist who studies neurogenesis.)

Methods of Neuropsychology

Gall's basic idea was pretty good, but his science was very bad (which is why we call phrenology a pseudoscience). Nobody takes phrenology seriously these days. However, evidence from neuropsychology favors Gall's idea of functional specialization, though not in Gall's particular form. The modern, scientifically based list of mental "faculties", and corresponding brain regions, is much different from his.

Neuropsychology offers a number of techniques for studying functional specialization.

Brain Lesions

Historically, the most important method for neuropsychology involves brain lesions, in which scientists observe the mental and behavioral consequences of damage to some portion of the brain.

In humans, this damage is almost always accidental, resulting from some insult, injury, or disease treated by neurologists.Obviously, ethical constraints prevent investigators from intentionally damaging the brains of their other humans, studies of neurological patients can provide valuable evidence about brain functions.

Sometimes, the lesions result from desperate medical procedures intended to alleviate disease, pain, or suffering. An example is the patient H.M., discussed below, who had his hippocampus and related structures destroyed in an attempt to control otherwise intractable epileptic seizures. At the time, the function of the hippocampus was unknown, and the surgeons were very careful to leave intact areas, such as the auditory projection area in the nearby temporal lobe, whose functions were known. It was only later that the surgeons and neuropsychologists realized that the hippocampus really did have a function -- and a rather critical one at that. This was because H.M. subsequently lost his ability to remember recent events -- indeed, anything at all that happened to him subsequent to his operation.

I'll have more to say about H.M. later in these lectures, and also in the lectures on Memory.

Link to an interview with Brenda Milner, who did the first experimental studies of H.M.

What Was It Like To Be H.M.? Henry Molaison was the subject of a great deal of important memory research, but all of those scientific papers gave readers little idea of what his life was like -- what it was like,that is, to have no memory.  Cognitive psychologists were very interested in H.M., but -- until Prof. Stanley Klein at UC Santa Barbara came along, hardly any personality or social psychologists took notice of him, or examined the implications of memory for identity, personality, and social interaction.  Klein never got to work with H.M., but his studies of other amnesic patients shed light on the structure of the self as a memory representation (e.g., Klein & Kihlstrom, Journal of Experimental Psychology: General, 1998).  Klein was also the first to note that amnesic patients have difficulty thinking of their personal futures, as well as their personal pasts, leading to the speculation that memory is the basis for mental time travel. One exception was Philip Hilts, a science journalist who made H.M. the centerpiece of his book on memory research: Memory's Ghost: The Nature of Memory and the strange Tale of Mr. M. (1996).   It is to Hilts that we owe H.M.'s description of his situation, moment to moment, day in and day out, as "like awakening from a dream". After H.M. died, in 2008, Suzanne Corkin, the neuropsychologist who had worked most closely with him over the years, beginning in (Brenda MIlner, a Canadian neuropsychologist who worked with Wilder Penfield, actually did the earliest research on H.M., published with Scoville in 1957; Corkin had been Milner's graduate student), published a sort of double "biography" covering both H.M's and her research program, entitled Permanent Present Tense: The Unforgettable Life of the Amnesic Patient H.M. (2013).  After all the research on H.M.'s memory, this is the first -- aside from Memory's Ghost.  Corkin reports that H.M.'s lesion also included part of his amygdala -- which, she speculates, may have been responsible for his relatively placid personality.   She writes (as quoted by Charles Gross, reviewing Corkin's book for The Nation, 11/04/2013): Buddhism and other philosophies teach us that much of our suffering comes from our own thinking, particularly when we dwell in the past and in the future....  Meditation is a method for training the mind to have a new relationship with time, knowing only the present....  Dedicated meditators spend years practicing being attentive to the present -- something Henry could not help but do. When we consider how much of the anxiety and pain of daily life stems from attending to our long-term memories and worrying about and planning for the future, we can appreciate why Henry lived much of his life with relatively little stress....  [A] part of us all can understand how liberating it might be to always experience life as it is right now, in the simplicity of a world bounded by thirty seconds. Some time thereafter, a kind of counterpoint appeared, in the form of another book, Patient H.M.: A Story of Memory, Madness, and Family Secrets by Luke Dittrich (a precis of sorts appeared in the New York Times Magazine ("The Brain That Couldn't Remember", 08/03/2016; see also the extensive review of the book by Seth Mnookin, a science journalist: "A Book Examines the Curious Case of a Man Whose Memory was Removed", New York Times Book Review, 09/04/2016).  Dittrich, as it happens, is the grandson of William Scoville, the neurosurgeon who performed the surgery on H.M. -- and, to make the story even better, his mother was Corkin's best friend in childhood.  Dittrich's book washes a fair amount of family laundry.  For example, he notes that his grandfather was a proponent of psychosurgery, and in particular prefrontal lobotomies, in cases of schizophrenia and other psychoses -- a procedure made infamous in Ken Kesey's One Flew Over the Cuckoo's Nest and other books and films.  But H.M.'s operation wasn't the usual sort of lobotomy.  Nobody thought that H.M. was psychotic, and nobody was trying to control his behavior through psychosurgery.  H.M.'s epilepsy apparently arose from his temporal lobe, and the surgery was an act of desperation to try to relieve him of the suffering of intractable seizures.  In both the magazine article and the book, and in subsequent interviews on the news media, Dittrich also made a number of charges concerning Scoville's motives in performing the surgery, and Corkin's mishandling of H.M. during his later career as a research subject.  By this time, Corkin herself had died, and couldn't defend herself. But MIT, where Corkin had been on the faculty, rebutted the most serious charges, and Corkin's colleagues (myself among them) wrote a strong letter to the Editor of the Times to protest Dittrich's treatment of her research.  So if you're interested in H.M., you should read this book; but you should also take its more spectacular claims with more than a grain of salt; and you should read Corkin's book as well. Another detailed biography of an amnesic patient is the Perpetual Now: A Story of Amnesia, Memory, and Love, by Michael D. Lemonick (2017).  Lemonick tells the story of Lonni Sue Johnson, who, when she was 57 years old, suffered the destruction of her hippocampus due to a viral infection.  As a result, she could no longer remember anything that happened to her more than about five minutes after the event.  Lemonick poses a good question about memory and identity: "If we have no memories of the experiences that made us, how can we know who we are?".

In laboratory experiments with nonhuman animals, brain tissue is sometimes deliberately destroyed, either surgically or by a relatively large jolt of electricity. For example, Philip Teitelbaum and his colleagues discovered that lesions in the ventromedial portion of the hypothalamus cause rats to overeat to the point of obesity (a syndrome known as hyperphagia), while lesions in the lateral portion of the same structure, the hypothalamus, cause rats to under-eat to the point of starvation or even death (a syndrome known as aphagia).

Findings such as these led to the conclusion that these two portions of the hypothalamus constitute "centers" for the initiation and termination of eating.In Teitelbaum's dual-center theory of eating behavior, the VMH inhibited eating, while the LH disinhibited eating. The two centers were arrayed antagonistically, so that activation of one inhibited the other.Destruction of the VMH released the LH from inhibition, leading to hyperphagia. Destruction of the LH, on the other hand, released the VMH from inhibition, leading to aphagia. The dual-center theory has now been significantly revised. Eating turns out to be more complicated than this, and it's certainly not the case that people with eating disorders, whether obese or anorectic, have lesions in one part or the other of their hypothalamus. The dual-center theory is offered here simply as a classic example of the way we can draw inferences from the results of lesions (and besides, Teitelbaum was one of my teachers in graduate school!).

Whether lesions occur accidentally or deliberately, they are, for all intents and purposes, permanent. Temporary lesions can sometimes be created by

But there are other techniques that do not cause permanent damage.

Electrical Stimulation

In electrical stimulation of the brain, a small electrical current is applied to some portion of the brain (or even a single cell) by means of a microelectrode implanted in brain tissue, and we observe the behavior or experience that results from that stimulation.

For example, Walle Nauta (1946) discovered that lesions in some portions of the reticular formation (in the upper brainstem, or midbrain) cause cats to fall permanently asleep, able to be awakened only by very loud sounds. Giuseppe Moruzzi and Horace Magoun (1949) discovered that electrical stimulation of these same regions caused cats to stay permanently awake (so long as the current is on). These observations led investigators to postulate the existence of a reticular activating system, centered on the reticular formation, which modulates levels of arousal and alertness.

As another example, James Olds and Peter Milner (1954) inserted microelectrodes into various locations in the brains of rats, and put the animals into an apparatus, commonly known as a 'Skinner box" (which I'll discuss later in the lectures on Learning), in which pressing a lever delivered a short burst of electrical current to that area of the brain -- in particular, a portion of the limbic system known as the "septal area".  It turned out that the rats would "work" feverishly to get these pulses, often to the exclusion of anything else.  This led the septal area, and especially the nucleus accumbens (abbreviated NAc), to be dubbed the "pleasure center" of the brain.  The NAc and ventral tegmentum (abbreviated VTA for Ventral Tegmental Area), another limbic-system structure, are major sources of the neurotransmitter dopamine, which is also involved in reward. Together, the NAc and VTA constitute a dopaminergic reward system that is heavily implicated in substance addiction. 

The functional specialization of various areas of the brain has been dramatically demonstrated by Josef Parvisi and his colleagues at Stanford (Kieran et al., Nature Human Behavior, 2020).  In the course or preparing neurological patients for surgery, they applied a matrix of microelectrodes directly to the surface of the brain.  After applying a small electrical current to individual electrodes, they asked patients to report their experiences.  The graphic provides a simplified view of the functional specializations revealed by this technique (taken from "The Brain Electric" by Christoph Koch, Scientific American, June 2021).  After stimulation in the occipital lobe, for example, a patient reported "I see a... blue and silver star".  Stimulated in the right parietal cortex, along the central sulcus, another patient reported a "pulsating feeling, mostly in the left chest but also in the left arm".  Stimulated in the corresponding area of the frontal lobe, a patient reported "I just had the urge to squeeze my fingers.  They just closed of themselves".  The resulting color-coded map, shows the exterior portion of the right hemisphere, the interior potion of the left hemisphere, and the underside of the brain, and shows a number of brain networks and systems devoted to motor processing vision, and the like.  

A variant on brain stimulation is transcranial direct current stimulation, or tDCS, in which a very small electrical current (about the equivalent of what is supplied by a standard 9-volt battery) is applied to electrodes attached to the scalp (thus, not to the brain directly).  A large number of positive effects have been claimed for tDCS, depending on where, and for how long, it is applied.  But most of these findings have not been replicated, so the actual effects of the technique, and any negative side-effects, are unknown at present.  Some vendors are offering consumer tDCS devices for home use, and some people have tried the simple expedient of attaching two wires to the terminals of a 9-v drugstore battery.  As they say, caveat emptor. 

For an interesting reviews of tDCS, see:

• "Transcranial Direct Current Stimulation: Five Important Issues We Aren't Discussion (but Probably Should Be" by J.C. Horvath et al. Frontiers in Systems Neuroscience (2014), a scholarly critique of tDCS research, see J.C.
• Horvath et al., "Evidence that Transcranial Direct Current Stimulation (tDCS) Generates Little-to-No Reliable Neurophysiological Effect Beyond MEP Amplitude Modulation in Health Human Subjects: A Systematic Review" (2015), a "meta-analysis" that yielded mostly negative findings.
• "Electrified" by Elif Batuman, New Yorker, 04/06/2015, a more personal, journalistic account.

Transcranial Magnetic Stimulation

Transcranial magnetic stimulation (TMS) is a variant on electrical stimulation, creating the functional equivalent of a temporary, reversible lesion in a discrete portion of brain tissue without requiring surgery to open up the scalp and skull (other techniques for creating temporary, reversible lesions, such as hypothermia and spreading depression, require surgical access to brain tissue). In TMS, a magnetic coil is applied to the scalp, and a magnetic pulse (which can approach the magnitude of 2 Tesla, about the strength of the MRIs used clinically, but not as strong as the pulses produced by the 4T machine used for research at UC Berkeley. The rapidly changing magnetic field induces an electrical field on the surface of the cortex. This field in turn generates neural activity which is superimposed on, and interferes with, the ongoing electrical activity of nearby portions of the brain. This temporary disruption of cortical activity, then, interferes with the performance of tasks mediated by parts of the brain near the site of application.

For example, TMS applied over a particular region of the occipital lobe interferes with visual imagery, supporting findings from other brain-imaging techniques that striate cortex is involved in visual imagery, as it is in visual perception.

Psychophysiology

Another method is to record physiological activity when people are engaged in particular forms of mental activity. Most psychophysiology focuses on measures of autonomic nervous system activity, such as measures of heart rate (the electrocardiogram, or EKG), blood pressure (the plethysmograph), and the electrical properties of the skin (the electrodermal response, or EDR, of which a good example is the skin conductance response, or SCR). There are also measures of somatic nervous system activity, such as the electromyogram (EMG). These measures will be familiar from crime dramas that use the polygraph as a lie detector (which, by the way, doesn't work very well).

But psychophysiology also includes measures of cortical activity, the most famous of which is the electroencephalogram (EEG). Because the brain is an electrochemical system, brain activity generates small electrical currents that can be recorded by electrodes placed on the scalp. Over the years, a number of different kinds of EEG activity have been recognized.

In ERP, as in conventional EEG, electrodes are placed on the scalp to record the electrical activity of the neural structures underneath. Then, a particular stimulus is presented to the subject, and the response in the EEG is recorded. If you present the stimulus just once, you don't see much: there are lots of neurons, and so there's lots of noise. But in ERP, the brain's response to the same (or very similar) stimulus is recorded over and over again: when all the responses are combined, a particular waveform appears that represents the brain's particular response to that particular kind of event.

The ERP has several components.

Interestingly, the characteristics of these components varies with the nature of the subject's mental activity.

ERPs can be recorded from the scalp as a whole, or they can be collected individually at lots of separate sites. In the latter case, the availability of powerful, high-speed computers permits a kind of brain-imaging: we can see where the ERP changes are the largest (or the smallest); and we can see how the ERP changes move with time. In this way, we can see how the brain shifts from one area to another when processing a stimulus or performing a task.

Brain Imaging

In brain imaging, techniques such as PET or fMRI (see below) are employed to literally watch the activity of various parts of the brain while subjects perform some mental task. For example, different parts of the brain "light up" when subjects examine a visual stimulus or listen to a tune.

Here are some combined MRI and PET images of the brain of a single subject engaged in different kinds of thinking, collected by Dr. Hanna Damasio of the University of Iowa College of Medicine, and published in the New York Times Magazine (May 7, 2000). Red areas indicate increased brain activation, as indicated by blood flow, while areas in purple indicate decreased brain activation.

Brain imaging has progressed quite a bit since those early days, and using fMRI, coupled with immense computational power and sophisticated processing algorithms, it is now possible to identify discrete patterns of neural activity associated with specific thoughts – or, at least, specific images.  In what I consider to be the most outstanding technical achievement of cognitive neuroscience to date, Jack Gallant and his group at UC Berkeley took advantage of the “topographical” organization of the visual system of the brain.  That is to say, each part of a visual stimulus projects onto a discrete portion of the retina of the eye, which in turn projects onto a discrete portion of primary visual cortex in the occipital lobe.  Gallant recorded activity in this portion of the brain while subjects viewed some 1,750 different pictures of natural objects, and then created a model representing each voxel (like a pixel on a computer screen, only three-dimensional) in the fMRI image acquired while the subject viewed each individual image.  They then recorded activity in this same area while the subject viewed 120 novel images, and attempted to identify which picture the subject was viewing, based solely on his pattern of brain activity, aggregated over 13 views of each image.

The amazing thing is that they were actually able to do this.  Based just on chance, we would expect these predictions to be accurate less than 1% of the time - -that is, 1 chance out of 120.  But in fact, their predictions were accurate 92% of the time in one subject, and 72% of the time in another subject.  Even when they considered only a single viewing trial, accuracy was far greater than we would expect just by chance – 51% in the one subject, 32% in the other.

  In a further experiment, Gallant and his colleagues ran their program “backwards”, as it were, and attempted to reconstruct the pictures themselves, based solely on the subjects’ pattern of brain activity.  In this slide, the target image is in the right-hand column, and the reconstructions, based on different algorithms, are in the others.  The reconstructions are far from perfect – this is cutting-edge work that pushes available technology to its very limits!  But they’re pretty good, and support the idea that every image, memory, and thought is represented in the brain by a unique pattern of neural activity.

Other investigators have used the same sort of technique to reconstruct spoken or imagined sentences.  

To my mind, Gallant's research is the most stunning technical achievement in neuroscience so far in the 21st century.  But its significance goes beyond our abstract understanding of how images (and, for that matter, thoughts) are represented in the brain.  It is also of potential practical importance. 

Of course, brains are active even if you're not thinking of anything in particular -- because you're always thinking of something, even if you're thinking about not thinking.  this constant background activity of the brain is known as the default mode, and is visible through brain imaging when a person is daydreaming, asleep, or even anesthetized.  The default mode itself involves a specific pattern of neural activity, not just randomness, known as the default mode network (DFN).  And the default mode is active indeed, consuming as much as 20 times the energy used in conscious mental activities -- which is why the DFN is sometimes referred to as the "dark energy" of the brain.  When we engage in some conscious mental activity, such as thinking pleasant or irritating thoughts, the brain shifts from this default mode into some other pattern.  Disruptions to the DFN may be implicated in a wide variety of mental illnesses, such as Alzheimer's disease or depression -- and even to thinking errors made by normal people in the ordinary course of everyday living.  

For more on the default mode network in the brain, see "The Brain's Dark Energy" by Marcus E. Raichle, one of the pioneers of functional brain imaging, in Scientific American, 03/2010.

Brain imaging techniques are gaining in popularity, especially in human research, because they allow us to study brain-behavior relations in human subjects who have intact brains. But still, some of the clearest evidence for mind-brain relations is based on the lesion studies that comprise classic neuropsychological research.

The fact that the nervous system operates according to certain electrochemical principles has opened up a wide range of new techniques for examining the relationship between brain and mind. Some of these techniques are able to detect lesions in the brain, without need for exploratory surgery or autopsy. Others permit us to watch the actual activity of the brain while the subject performs some mental function.

CT (CAT) Scans. In x-ray computed tomography (otherwise known as CAT scan, or simply CT), x-rays are used to produce images of brain structures. This would seem to be an obvious application of x-ray technique, but there are some subtle problems: (1) radiation can damage brain tissue; (2) brain tissue is soft, and so x-rays pass right through it; and (3) x-rays produce two-dimensional images, and so it is hard to distinguish between overlapping structures (that is, you can see the edges of the structures, but you can't detect the boundary between them). The CT scan uses extremely low doses of x-rays, too weak to do any damage, or to pass through soft tissue. It also takes many two-dimensional images of the brain, each from a different angle. Then a computer program takes these hundreds of individual two-dimensional images and reconstructs a three-dimensional image (this requires a very fast, very powerful computer). CT scans allow us to determine which structures are damaged without doing surgery, or waiting for the patient to die so that an autopsy can be performed.

Magnetic Resonance Imaging (MRI). The technique of magnetic-resonance imaging (MRI) is based on the fact that some atoms, including hydrogen atoms, act like tiny magnets: when placed in a magnetic field, they will align themselves along lines of magnetic force. Bombarding these atoms with radio waves will set them spinning, inducing a magnetic field that can be detected by sensitive instruments. In a manner similar to CT, readings from these instruments can be used to reconstruct a three-dimensional image of the brain. However, this image has a much higher resolution than CT, and so can detect much smaller lesions.

MRI is such an important advance in medical technology that Nobel prizes have been awarded on several occasions for work relating to it. The 2003 Nobel Prize for Medicine or Physiology was awarded to Paul C. Lauterbur, a physical chemist at the University of Illinois, and Peter Mansfield, a physicist at the University of Nottingham, in England, for basic research that led to the development of the MRI. Lauterbur published a pioneering paper on 2-dimensional spatial imaging with nuclear magnetic resonance spectroscopy (when NMR was picked up by medicine, the word "nuclear" was dropped for public-relations reasons, so that patients would not think that the technique involved radiation -- which it doesn't). Mansfield later developed a technique for 3-dimensional scanning. Eager young scientists should note that Lauterbur's paper was originally rejected by Nature, although the journal eventually published a revision. And if that's not inspiration enough, Mansfield dropped out of the British school system at age 15, returning to college later; now he's been knighted!

Some controversy ensued because the prize committee chose not to honor the contributions of Raymond Damadian, a physician, inventor, and entrepreneur, who made the initial discovery that cancerous tissue and normal tissue give off different magnetic resonance signals. Damadian also proposed that it be used for scanning tissues inside the body, and made the first working model of a MR scanner (now on display in the Smithsonian National Museum of American History). Damadian subsequently took out expensive full-page advertisements in the New York Times and other publications to assert his priority. But even before Damadian, Vsevolod Kudravcev, an engineer working at the National Institutes of Health, produced a working MRI device in the late 1950s by connecting an NMR to a television set: his supervisor told him to get back to his assigned job, and nothing came of his work. (See "Prize Fight" by Richard Monastersky, Chronicle of Higher Education, 11/07/03).

The Nobel committee, following its tradition, has been silent on its reasons for excluding Damadian. Everyone seems to agree that Lauterbur and Mansfield's work was crucial to developing MRI as a clinically useful technique. Still, no one doubts the importance of Damadian's pioneering work, either, and the Nobel rules make room for up to three recipients of a prize. The decision may just reflect an admittedly unreliable historical judgment. On the other hand, science has its political elements, and there could have been other reasons for denying Damadian the prize. It is possible that Damadian was denied the prize because he is a practicing physician and business entrepreneur rather than an academic scientist. Perhaps because he is relentlessly self-promoting (as in his newspaper as, which are without precedent in Nobel history), and famously litigious (he won a settlement of $129 million from General Electric for patent infringement) and rubs people the wrong way. Perhaps the Nobel committee did not want to give an award for biology, and thus at least indirect legitimacy, to someone who rejects the theory of evolution, the fundamental doctrine of modern biology, believes in a literal reading of the Bible, and has lent his support to creationism.

Positron Emission Tomography (PET). CT and MRI are new ways of doing neuroanatomy: they help us to localize brain damage without resort to surgery or autopsy. And that's important. But we'd also like to be able to do neurophysiology in a new way: to watch the brain in action during some mental operation. A technique that permits this is positron-emission tomography (PET). This technique is based on the fact that brain activity metabolizes glucose, or blood sugar. A harmless radioactive isotope is injected into the bloodstream, which "labels" the glucose. This isotope is unstable, and releases subatomic particles called positrons; the positrons collide with other subatomic particles called electrons, emitting gamma rays that pass through the skull and, again, are detected by sensitive instruments. When a particular portion of the brain is active, it metabolizes glucose, and so that part of the brain emits more gamma rays than other parts. Fast, powerful computers keep track of the gamma-ray emissions, and paint a very pretty picture of the brain in action, with different colors reflecting different levels of activity.

Functional MRI (fMRI). This is a variant on MRI, but with a much shorter temporal resolution than standard MRI. Like PET, it can be used to record the activity of small regions of the brain over relatively small intervals of time. However, the temporal resolution of fMRI is smaller than that of PET, permitting investigators to observe the working brain over shorter time scales. Whereas most brain-imaging studies have to "borrow" time on machines intended for clinical use, UC Berkeley has a very powerful fMRI machine dedicated entirely to research purposes.

Diffusion Tensor Imaging (DTI) or Diffusion Spectrum Imaging (DSI) is a variant on fMRI, and complements fMRI in several ways. Whereas fMRI tracks the flow of blood in the brain, and indicates activity in the "grey matter", or neurons that comprise the surface sheet of the cerebral cortex, DTI tracks the movement of water and indicates the activity of the "white matter", the long axons that connect various locations in the brain. While fMRI can reveal distinct brain centers that are involved in various functions, DTI can reveal how distinct brain centers link with each other in systems.This DTI image, looking down on a mammalian brain from the top, shows three different groups of fibers:

Here, in an image taken from American Scientist (9-10/2010) is a DSI image of a cat's brain at 10 days of age, and again at 3 months, you can see the dense interconnections characteristic of the mature mammalian brain.

The interconnections between different brain regions are implicated in traumatic brain injury induced by forceful blows to the head, such as those sustained in vehicle accidents, on the football field, and and in explosive blast injuries suffered by service-members in the Iraq and Afghanistan wars.

Beginning in 2010, the NIH Human Connectome Project, modeled after the Human Genome Project, has begun a project to use various histological and imaging techniques to trace the connections between various parts of the brain (so far, they've succeeded in tracing all the connections in the nervous system of a worm species with only 300 neurons. The next step is to perfect their techniques with the 100 million neurons of the mouse brain, before getting to the 100 billion neurons of the human brain. For the present, human connectome researchers have to be content with tracing the connections between larger areas of the brain.

Functional Specialization in the Brainstem

We've already seen examples of functional specialization at the cell and tissue levels.

We've already seen examples of functional specialization in the hindbrain and midbrain:

The midbrain is involved in two neurological syndromes:

Functional Specialization of Subcortical Structures

The principle of functional specialization continues in the subcortical structures of the forebrain.

We have already discussed the hypothalamus, a structure in the diencephalon that is involved in eating and other biological motives.

And we already introduced Patient H.M.,

H.M, whose severe epilepsy led to a desperate surgical procedure involving the excision of the medial (interior) portions of his temporal lobe -- an operation that also excised his hippocampus and portions of the limbic system. After the surgery, H.M. displayed a retrograde amnesia for events occurring during the previous years prior to the surgery. But more important, he displayed an anterograde amnesia for all new experiences. He could not remember current events and he could not learn new facts. The retrograde amnesia remitted somewhat after the surgery, but the anterograde amnesia persisted until his death in 2008, at the age of 82. H.M. remembered nothing of what happened to him since the day of his surgery in 1953, when he was about 27 years old. He read the same magazines, and worked on the same puzzles, day after day, with no recognition that he had done them before. He met new people, and participated in an extensive series of experiments to document the extent of his memory loss, but when he met the experimenters and other visitors again he did not recognize them as familiar. He knew nothing about the deaths of his parents, the Vietnam War or the War in Iraq, the assassination of President Kennedy or the election of President Obama.

Work with H.M. and similar patients reveals a brain system important for memory. This circuit, known as the medial temporal-lobe memory system, (MTL) includes the hippocampus and surrounding structures in the medial portion of the temporal lobe. This circuit is not where new memories are stored. But it is important for encoding new memories so that they can be retrieved later. H.M. lacks this circuit, and so he remembers nothing of his past since the surgery.

H.M.'s real name was Henry Molaison. He was born on February 26, 1926, had his operation on September 1, 1953, and died on December 2, 2008. He received a beautiful obituary in the New York Times, which called him a "memorable patient" (12/04/2008). For an insightful portrayal of H.M.'s life, read Memory's Ghost: The Nature Of Memory And The Strange Tale Of Mr. M  (1995) by Philip J. Hilts, and also Permanent Present Tense: The Unforgettable Life of the Amnesic Patient. H.M. (2013) by Suzanne Corkin, a neuropsychologist who worked with H.M. almost from the beginning of his "career" as the world's most famous neurological patient.

Another example comes from the patient S.M., who suffered damage to the amygdala, another subcortical structure, but no damage to the hippocampus and other structures associated with the medial temporal lobes. This resulted from a rare medical condition, lipoid proteinosis, that results in the calcification, and eventual disappearance, of the amygdala but no other brain structure (something about the neural tissue that makes up this structure, apparently). S.M. suffers no memory deficit, nor any other problems in intellectual functioning. But she does display gross deficits in emotional functioning: a general loss of emotional responses to events, especially fear; an inability to recognize facial expressions of emotion, especially fear, as well as difficulties distinguishing among negative emotional expressions; and an inability to produce appropriate facial expressions herself. Research on S.M. and similar patients suggests that the amygdala is part of another brain circuit that is important for regulating our emotional life, particularly fear.

Interestingly, S.M. does experience panic.  In an experiment by Wemmie et al. (2013), she inhaled carbon dioxide in amounts sufficient to cause feelings of suffocation (sort of like waterboarding without the waterboard, I suppose).  She didn't do it for very long, so no actual harm was done, but the interesting thing is that S.M. experienced a flood of fear.  This is implies that, however much the amygdala is involved in fear, it is not the only such structure.

It is often claimed that the amygdala is the seat of our emotions, but most of the research on the amygdala involves fear and anger -- components of Cannon's "flight or fight" syndrome.  It's not yet clear that the amygdala plays a similar role in other emotions, such as joy, surprise, sadness, and disgust.  In fact, affective neuroscientists have begun to trace links between these emotions and other brain structures.

Functional Specialization in Cerebral Cortex

Turning from subcortical structures to the cerebral cortex itself, we find that different areas also have specialized functions. Some of these have been revealed by studies of neurological patients who have suffered from strokes. In stroke, there is a blocking of an artery, and a consequent loss of blood supply to one or another portion of the brain. This in turn causes a lack of oxygen (carried by the blood), and the death of brain tissue in the area of the brain served by the artery. This, in turn, causes a loss of function such as paralysis (inability to make voluntary motor movements), tactile anesthesia (inability to feel touch or pain), and aphasia (loss of speech functions).

If we examine a map of the vascularization of the brain, we see that a number of major arteries run up the central fissure separating the frontal and parietal lobes. This finding suggests that these areas are important for movement, touch, and speech. The sensorimotor areas are areas of the frontal and parietal lobes immediately surrounding the central fissure.

Primary Motor and Somatosensory Areas

Viewing the interior portion of the cerebral cortex, "sliced" vertically at the central fissure, the brain opens up to reveal the cerebral commissure at the top, the cortical areas adjacent to the central fissure in the middle, and the fold along the lateral fissure at the bottom.

This portion of the frontal lobe, known as the precentral gyrus (because it is in front of the central fissure) or Brodmann's Area 4, the comprises the primary motor area of the brain, which controls voluntary movement of various body parts. There is also a premotor cortex, a kind of secondary motor area, comprising Brodmann's areas 6 and 8), just anterior to the primary motor area.

Similarly, the corresponding portion of the parietal lobe, known as the postcentral gyrus or Brodmann's Areas 1-3, comprises the primary somatosensory area of the brain, which controls the sensation of touch, heat, and cold in various body parts.

The motor homunculus (from the Greek, freely translated as "little man in the head") represents the regular association between the location of a particular body part, and the cortical site that controls its motor activity. The legs and feet are controlled by portions of the frontal lobe tucked inside the longitudinal fissure; the trunk and arms and hands along the upper surface of the frontal lobe, along the central fissure; the face is there too, right near the temporal lobe; and the vocal apparatus is tucked inside the lateral fissure. Note that the amount of cortex dedicated to each are of the body is proportional to the need of that body part for precise motor control. There is also a "speech area" in the frontal lobe, adjacent to the motor areas controlling the mouth, tongue, throat, and larynx: more about this later.

Similarly, the sensory homunculus represents the regular association between the location of a particular body part, and the cortical site that receives tactile sensations from that body part: the feet are near the legs, adjacent to the longitudinal fissure, the hands are near the arms, adjacent to the central fissure, with the trunk is in between them; the face is near the temporal lobe, near the lateral fissure; and the internal organs are tucked inside the lateral fissure. Again, there is proportional representation, with greater amounts of cortical tissue devoted to those body parts (like the hands and feet) that make fine tactile discriminations.

Primary Auditory and Visual Areas

In addition, a portion of the temporal lobe is the primary auditory projection area, or A1 (A-one), is specialized for auditory function (this area is also known as the superior temporal gyrus, or Heschl's gyrus, and includes Brodmann's areas 41 and 42. A1 is characterized by "tonotopic"organization, meaning that different portions of auditory cortex correspond to different auditory frequencies, or pitches.

Similarly, a portion of the occipital lobe is the visual projection area (also known as VI, or striate cortex, corresponding to Brodmann's area 17, is specialized for visual function.VI is characterized by "retinotopic" organization, meaning that different portions of striate cortex correspond to different portions of the retina of the eye.

Certain visual functions are also performed by the extra-striate cortex of the occipital lobe, including Brodmann's areas 18 and 19.

In fact, the visual area itself is very complex, consisting of several different areas and circuits, each performing different functions. For example, there is one visual area specialized for color, and another specialized for motion.

Association Cortex

The remaining portions of the brain were once thought to be largely undifferentiated association areas involved in "putting things together": sensory and sensory-motor integration, learning, memory, thinking, and language. As a general rule, the posterior association area is specialized for perceptual integration, linking he visual, auditory, and tactile centers in the occipital, temporal, and parietal lobes. By the same token, the frontal association area, is specialized for problem-solving and strategically organized activity ("executive functions").

The prefrontal cortex (so called because it consists of frontal areas forward of the motor strip) is especially well developed in humans: we devote a great deal of our cortical matter to complex intellectual functions.Prefrontal cortex includes the superior, middle, and inferior frontal gyri, and the superior and inferior frontal sulci separating them.

The prefrontal cortex is commonly thought to be the brain location of executive control functions -- including the control of our emotions. During times of stress, the release of norepinephrine and dopamine during the "flight or fight, tend and befriend" response stimulates the activity of the amygdala, but inhibits the functioning of the prefrontal cortex. So, our emotional states (mediated by the amygdala and other structures) are not just more intense than they would be otherwise; they are also less subject to executive control. This, apparently, is what happens when, under acute stress, we "lose it" or choke under pressure [see "This is Your Brain in Meltdown" by Amy Arnsten, Carolyn M. Mazure, and Rajita Sinha, Scientific American, 04/2012].

However, the notion of "association areas" is a little misleading, because it implies that most of the brain is a general-purpose information processor. In fact, neuropsychological studies suggest that there is a lot of specialization within the "association areas" as well. Consider the wide variety of neurological syndromes that have psychological consequences:

There are various subtypes within each of these syndromes, each of which is associated with a different site of brain damage, or involving several different sites organized into a circuit or system.

We see this combination of specialization and integration in the various forms of aphasia, involving loss or impairment of various speech and language functions.

In neither case is there any damage to the corresponding skeletal musculature: the source of the psychological deficit resides in specific lesions in the central nervous system.

Based on evidence such as this, it seems that linguistic communication requires the coordination of several centers. It turns out that Broca's and Wernicke's areas are connected by a bundle of nerve fibers. According to one account, the structure of the person's speech utterance is encoded in Wernicke's area, which also decodes the utterances of others. The encoded utterance is transferred to Broca's area, which organizes vocalization. These "instructions" are then transferred to motor areas which actually produce speech and writing  Speaking a written word recruits different brain areas than speaking a spoken word (Posner et al., 1988; Petersen et al., 1989).

Much the same point is made by a recent study by Robert Knight’s group at UC Berkeley.  Working with patients being prepared for neurosurgery, they placed a grid of 64 electrodes directly onto the surface of the brain, a technique called “electrocorticography”, and then recorded brain activity at each of the sites while the subjects performed a simple linguistic task: they were given a noun, such as “cake”, and had to produce an associated verb, such as “bake”.  This slide is animated, and when you push the “play” button, you’ll see what they saw, except you’ll see it in slow motion.  When the stimulus is presented, the auditory cortex is activated first, followed immediately by Wernicke’s area, as the subject decodes the word and searches for an association; then Broca’s area is activated to organize the response, which is finally executed by that part of motor homunculus that controls the speech apparatus.

If you watch the animation carefully, though, you’ll also see some other things going on.  In the first place, Broca’s area is also activated when the stimulus is presented, as if the speech apparatus is involved in speech perception as well as speech production.  And Wernicke’s area is activated when the response is spoken, as if the subject was checking his response.  So while we generally think of Broca’s area as specialized for speech production and Wernicke’s area for speech perception, things are actually a little more complicated than that.  But the basic point is that even very simple actions require the coordinated activity of a number of different specialized centers.

Here's another example, this time involving memory.  John Anderson and his colleagues used magnetoencephalography (MEG, a variant on EEG) to record brain activity while subjects performed a simple memory task: recognizing a word with which another word had been paired, or the answer to an arithmetic problem (Psych. Sci., 2018).  The two tasks gave strikingly similar results.  Over the course of a very short period of time (a little more than a second), Anderson et al. observed activation in the occipital cortex during encoding of the visually presented cue; then in the temporoparietal junction (TPJ) while the subjects searched memory, the prefrontal cortex while deciding on a response (yes or no), and finally the left motor cortex while making their response (with a finger of their right hand).  Again, the point is that in most interesting tasks, various parts of the brain work together, in a coordinated manner, to analyze the situation and respond appropriately.

Visualizing Seeing and Speaking Using modern brain-imaging techniques such as fMRI and EEG, we can actually watch the brain in action while subjects perform various tasks, and see the interplay among the various regions.  This was anticipated, in a way, by Fritz Kahn (1888-1968), a German physician who was a pioneer in data visualization, or what we would now call infographics.  In his 1939 book, Der Mensch Gesund und Krank (Human Health and Illness), Kahn depicted seeing and speaking in mechanical terms.  A person sees an automobile (1), the visual image is encoded by the eye (2) and transmitted to the visual cortex (3) where the image is formed, then to the parietal lobe (4) for identification and classification, then to the frontal lobe (5) to prepare the speech act, then out the efferent apparatus (6) to the vocal cords (7), resulting in the spoken word "auto" (8). OK, so some of the details aren't quite right.  We know more about how the brain works than we did in the 1930s. And besides, when someone once told Kahn that some of his drawings were inaccurate, he defended his work on the grounds that his images made things more easily understandable.

Here are some other examples of functional specialization:

An area of the medial temporal lobe known as the fusiform gyrus (Brodmann's area 37) appears to be specialized for face recognition.

Results like these have led some cognitive neuroscientists to label the fusiform gyrus as the fusiform face area (FFA). This move is somewhat controversial, because there is some evidence that the recognition deficits in prosopagnosia are not specific to faces, but can extend to other kinds of objects. In addition, the FFA also is activated by other kinds of recognition tasks. The details of the debate are not important for present purposes: in either case, the fusiform gyrus seems to be specialized, either for face recognition (as the fusiform face area) or for a more general category of recognition of which face recognition is a good example (as a "flexible face area").

A part of the limbic lobe known as the anterior cingulate gyrus, or anterior cingulate cortex (ACC), appears to play an important role in self-regulation. The precise function of ACC is still subject to debate. According to one theory, it detects errors in responding, so that they can be corrected; according to another, it monitors conflict between responses, so that the conflict can be resolved. In either case, ACC is involved in executive functions generally associated with controlled, deliberate (as opposed to automatic) processing.

A portion of the parietal lobe near the temporoparietal junction (TPJ), where the temporal and parietal lobes meet, plays an important role in attention. For example, a neurological syndrome known as hemispatial neglect often follows damage to this region of the parietal lobe. In hemispatial neglect, the patient seems to ignore that portion of space which is opposite (contralateral) to the patient's lesion. Thus, if asked to bisect a horizontal line, a patient with a lesion in the right TPJ may draw his or her line only about 1/4 of the way in from the right. It is as if s/he doesn't see the left half of the line: but the patient's visual system is intact. It is as if there were a kind of "magnet" that draws the patient's attention away from one portion of space. Neglect is more common in patients with lesions in the right TPJ, creating neglect in the left portion of space (more about this shortly) -- which suggests that it's the right TPJ that is particularly specialized for attention.

The truth be told, attention is a complicated business. As with repeating written and spoken words (discussed above), attention provides an opportunity to show how different parts of the brain, each performing their own specialized function, act together in an integrated fashion.

According to a stage model of attention proposed by Posner and his colleagues, "paying attention" to something actually involves a sequence of activities.

The Doctrine of Modularity

While it was once thought that the brain was a general-purpose information processor which forms associations between stimuli and responses, we now know that the brain is highly specialized -- a situation characterized by the philosopher Jerry Fodor (1983) as the modularity of mind. The basic idea behind modularity is that different mental functions are served by specific mental "organs" that are dedicated to those particular purposes; these mental organs are, in turn associated with different brain structures or systems -- for example, the medial temporal lobe memory system involved in memory, or the language system that includes Broca's and Wernicke's areas.

This is, of course, the central tenet of the fundamental neuroscientific doctrine of functional specialization. But there's more. According to Fodor, mental modules have a number of properties in common:

Fodor's theory is an extreme view of modularity, and its details are controversial. For example, it may be that some modules are not innate, but rather develop as a result of certain learning experiences. Still, the general principle that different mental functions are served by different "mental organs", which in turn are associated with different brain structures (or systems), is quite widely accepted within psychology, cognitive science, and cognitive neuroscience.

The result is a map of cortical specialization that looks something like the old phrenological head, but with different faculties and, where the old and new lists of faculties happen to overlap, different locations. This figure, which appeared in the New York Times in 2000, shows how much progress had been made in localizing various functions in the brain by that time, based mostly on neuropsychological studies of brain-damaged patients, studies of animals, and neuro-imaging studies (mostly employing PET and fMRI). The comparison with the traditional phrenological head is striking: the phrenologists had the right idea about functional specialization, but they got every single detail wrong.

The Human Connectome

The Doctrine of Modularity represented an important corrective to the traditional view that the brain -- or, at least, "association cortex" -- functioned as a general-purpose information-processing device.  Rather, it appears that some cognitive tasks are performed by dedicated mental modules that are associated with a fixed neural architecture -- Wernicke's and Broca's areas for speech and language, the hippocampus and the medial temporal lobes for memory, etc.  At least since the case of H.M., something like the Doctrine of Modularity has guided neuropsychology for decades: If you think about it, it doesn't make any sense to use a technique like fMRI to look for task-specific patterns of brain activation unless there are task-specific modules located in specific areas of the brain.  And the Doctrine of Modularity continues to generate interesting findings on the neural bases of various mental functions. 

At the same time, neuropsychologists have come to appreciate the Doctrine's limitations.  For example, many forms of mental illness, such as schizophrenia, depression, anxiety disorder, and autism do not seem to be associated with lesions in discrete brain modules, as revealed by patterns of brain activation (or, for that matter, deactivation) -- as is the case, for example, with such neurological disorders such as aphasia and amnesia -- or even Alzheimer's disease.  More important, at a theoretical level, it's clear that these brain modules are not, in fact, as independent as the Doctrine would seem to suggest.  The conventional view of modularity is that the brain is like a sort "Swiss Army knife", which contains a whole bunch of independent tools bound together in a single package (like the skull).  On the contrary, it's clear that the various brain modules work together.  So, they have to be connected to each other, so that they can pass information among themselves -- much like the examples of speaking spoken and written words discussed earlier.  Having a conversation is going to require modules for speech perception, syntactic analysis, semantic memory, thinking, and speech production, all integrated with each other.

Put another way, the brain may be a collection of specialized modules, but these modules have to interact with each other, and this interaction requires that they be connected to each other in an integrated system.  The most recent trend in neuropsychology and neuroscience has been to focus on the connections by which different modules pass information from one to each other.  As important as this new focus will be for theory, researchers also hope that it will help unlock the neural bases of various forms of psychopathology.  It may be, for example, that the problem in schizophrenia or autism is not with a specific mental module (or two or three), but rather with the connections between them.  Alzheimer's Disease, with its plaques and tangles, may well prove to be a problem of dysfunctional connections.  These dysfunctional connections, if indeed they exist, will not be observable with conventional fMRI, but may well yield to other techniques like Diffusion Tensor Imaging (DTI) or Diffusion Spectrum Imaging (DSI), variants on fMRI which pick up activity in the white matter which makes these connections. 

When you consider that the human brain has about 80-100 billion neurons, with more connections among them than there are stars in the sky, this is going to be quite a project.  So, it's going to start slowly.  Here's one road map to the human connectome:

In 2013 the Obama Administration announced a new BRAIN initiative (Brain Research through Advancing Innovative Neurotechnologies).  A major element in the BRAIN Initiative is the "Human Connectome Project" (the allusion to the Human Genome Project is intentional), a public-private collaboration involving the National Institutes of Health, the National Science Foundation, and other federal agencies focused on mapping the connections in the brain.

The resulting Brain Activity Map is intended to show how the brain is wired up, at all levels of analysis from pathways among lobes, ganglia, and Brodmann's areas to the links between individual nerve cells.

For more information on the connectonomics and the Human Connectome Project, see Connectome by Sebastian Seung (2012).

A New Map of the Brain -- and a New Guide for Identifying Functional Specializations

For a long time, the brain was mapped in terms of topographical features such as the lobes, fissures, sulci, and gyri visible on the surface of the cortex; and also, based on histological examination, in terms of Brodmann's areas. 

• For, example, neuroanatomists might refer to the "temporal pole" (the anterior portion of the temporal lobe), or to Brodmann's area 38. 
  
• Alternatively, when the psychological function of some particular brain area had been identified, they might refer to something like "Broca's area" (which is linked to speech production), located in the inferior frontal gyrus, corresponding to Brodmann's areas 44 and 45.
  
• The so-called "fusiform face area", ostensibly specialized for recognizing faces, is located in the lateral portion of the fusiform gyrus, on the ventral (lower) surface of the temporal lobe, corresponding to Brodmann's area 37.

And these maps have served us well in identifying various functional specializations in the brain.

More recently, however, a newer approach has delivered a revised map or parcellation of the brain, based on the simultaneous use of a number of different methods.  Glasser, Van Essen, and their colleagues in the Human Connectome Project (HCP) took information based on brain topography (e.g., sulci and gyri), architecture (e.g., cortical thickness and relative myelin content), function (e.g., Broca's area or the (fusiform face area"), and connectivity (as determined by diffusion tensor imaging). 

Around the turn of the 20th century, Brodmann (1909) had identified about 50 areas; toward the end of the century, neuropsychological and brain-imaging studies of functional specialization had brought that total up to about 83.  Combining the four methods, Glasser, Van Essen, et al. identified 97 new areas, for a total of 180 distinct areas in each hemisphere.  They call this the HCP Multi-Modal Parcellation, Version 1.0 (HCP_MMP1.0) -- implying that, at some point in the future, they'll release Version 2.0, presumably identifying even more areas? 

In 2021, the journal Nature published a set of 17 articles announcing a new atlas of the brain sponsored by the BRAIN Initiative (see above), and spearheaded by a group of molecular and cellular neuroscientists at UCB.  These studies sampled various properties of neurons in the primary motor cortex (Brodmann Area 4) -- not just their histology but other factors such as what genes they express and what neurotransmitters they release, whether they are excitatory or inhibitory, etc.  The investigators used a statistical technique called cluster analysis to sort the neurons into various categories.  Although they all may looked alike to Brodmann, it turns out that there are lots of different types of neurons even in this fairly narrowly circumscribed area.  One group, illustrated in the image on the left, projects from the primary motor cortex to the brainstem. 

Put another way: from a histological perspective, all the neurons in the primary motor area, the precentral gyrus, look alike; but they're not.  Whether the actual number of different types of neurons is 12 or 116, it's clear that the anatomical structure of the brain is a lot more complicated than we thought it was.  Whether all these different types of neurons have different mental and behavioral functions is another question.  That's a problem for psychologists to solve using the standard techniques of behavioral science.  Link to a press release (10/06/2021) announcing the new discoveries.

Mapping the brain is one thing, but for psychologists the important question is whether these areas are differentiated with respect to function.  If you look, you can see, among other specialized areas, Broca's area in the left frontal lobe, Wernicke's area in the left temporal lobe, and the so-called "fusiform face area" in the temporal lobe.  And in fact, Glasser, Van Essen, et al. have already identified a new area, #55b in the frontal lobe, that appears to be active when people are listening to stories.

More work of this type will go on, using standard brain-imaging methodologies to identify, or more precisely delineate, various functional specializations.  But it's important to remember that the brain isn't just a kit of tools that more or less operate independently.  The brain is an integrated organ, with lots of different parts working together to perform various tasks.  For example, here is a depiction of the areas of the brain, including the new area 55b, which are activated (or, in some cases, deactivated) when subjects listen to stories.

Recent work by Max Bertolero and Danielle Bassett have produced a new functional map of the brain by drawing (no pun intended) on graph theory, in a field known as network neuroscience (Nature Human Behaviour 2018; Scientific American, 07/2019; Bertolero took his PhD in systems neuroscience from UC Berkeley).  Based on a survey of thousands of brain-imaging studies employing fMRI, B&B identified 7 key modules in the brain dedicated to such functions as vision, attention, self-control, and the like.  Interestingly, as depicted in the accompanying figure (taken from their SciAm article) these modules are sometimes spread across disconnected areas of the brain -- a departure from the implications of the traditional Doctrine of Modularity.  Anyway, each module can be thought of as a collection of nodes, with the module itself represented by the "edge" formed by the links among the nodes.  Some of these nodes connect only to other nodes in a given module; other nodes, known as connector hubs, also link to nodes in other modules.  Although each module can function independently of the others, most complex tasks require activity in more than one module: thee connector hubs allow different modules to communicate with each other.  The resulting graph, also depicted in the figure, integrates insights from the Doctrine of Modularity and the Human Connectome Project to show how various modules are connected with each other, providing the neural substrate of mental activity. 

One implication of this view of the brain is to demolish, once and for all, the old canard that we only use 10% (or 50%, or whatever) of our brains.  We use all of our brains, all of the time, with the pattern of activity differing from task to task. 

• Even within a task, however, B&B claim, on the basis of ongoing research by the Human Connectome Project, that each individual has a unique pattern of activity -- an almost fingerprint-like signature of the individual's brain in action. 
  
• Changes in both structural (i.e., between actual physical neurons) and functional (i.e., between nodes in B&B's graph structure) occur throughout the life cycle, particularly in childhood and adolescence, but also in the elderly.
• Connectivity is also affected by the environment (rich or impoverished), and by opportunities for learning.
• And problems with connectivity may be responsible for some forms of mental illness.  In schizophrenia, for example, B&B suggest that brain networks are hyperflexible, able to reconfigure themselves in unexpected ways -- so that, perhaps, links between the modules for speech and audition connect themselves up to produce auditory hallucinations, in which the patient experiences his or her own "internal speech" as coming from the external world.  In depression, a disconnection between the self-regulatory module and the module for emotion may lead to the dominance of recurrent, negative thoughts.  You get the idea.

Lateralization of Function

The specialization of function extends to the two cerebral hemispheres, right and left, created by the central commissure, or corpus callosum. Anatomically, these two hemispheres are not quite identical: on average, the left hemisphere is slightly larger than the right hemisphere. 

Most psychological functions are performed by both hemispheres, but there is some degree of hemispheric specialization as well.

Contralateral Projection

One aspect of hemispheric specialization is known as contralateral projection, meaning that each hemisphere controls the functions of the opposite side of the body. Thus, the right hemisphere mediates sensorimotor functions on the left part of the body, auditory function of the left ear, and visual function of the left half-field of each eye. The left hemisphere does just the opposite. The two hemispheres communicate with each other, and integrate their functions by means of the corpus callosum, a bundle of nerve fibers connecting them.

"Split Brain" Patients

Contralateral projection is vividly illustrated by so-called "split-brain" patients. These patients suffer from severe, intractable epilepsy. In an effort to help control their seizures, their corpus callosum and other transcortical connections have been severed -- so that, at least, seizure activity arising in one hemisphere cannot pass over into the other hemisphere. This surgery has no negative consequences for their normal behavior, but careful laboratory experiments by Sperry, Gazzaniga, Bogen, and their colleagues have revealed some interesting anomalies (the work by Sperry, Gazzaniga, and Bogen helped win the Nobel Prize in Physiology or Medicine for Sperry, honoring his work on the functional specialization of the cerebral hemispheres -- a prize which he shared with David Hubel and Torsten Wiesel, whose work we will discuss later).

Link to an interview with Michael Gazzaniga.

Consider, for example, a split-brain patient who is asked to fixate on a dot in the middle of his visual field; then a picture of a horse is presented in his left visual field.

Similarly, imagine that the word key is presented in in the left visual field, and the word ring is presented in the right visual field.

Observations such as this have suggested to some theorists that the conscious awareness is localized in the left hemisphere, and that the right hemisphere operates unconsciously, outside of conscious awareness. But that's a mistake. The right hemisphere is conscious, just as the left hemisphere is, but it simply can't express its conscious awareness verbally, because it doesn't have the necessary centers for speech and language.

Genesis and Agenesis of the Corpus Callosum

Kim  Peek (1951-2009), a "savant" who inspired Raymond Babbitt, the autistic character played by Dustin Hoffman in the movie "Rain Man" (1988), was not himself autistic, but he was born without a corpus callosum -- an anatomical defect that, apparently, permitted him to read facing pages of a book at once, one page with each eye. He also had a number of other remarkable abilities, such as an ability to recall obscure facts across a wide range of topics (Photos by Barton Glasser/Deseret News, via Associated Press, and United Artists, from the obituary by Bruce Weber, New York Times, 12/27/2009).

This condition, known as agenesis of the corpus callosum, occurs in 1 out of about 4,000 infants, and is especially prominent (about 7%, which is a lot more than 0.03%) in children with fetal alcohol syndrome.  The typical result is a severe delay in the development of various verbal and motor skills.  This is not surprising, because the corpus callosum is the principal "highway" connecting the two hemispheres, and a disruption in its functioning will severely hamper the coordination among various brain centers. 

However, it is possible to compensate for the absence of a corpus callosum.  Under ordinary conditions -- not the laboratory setups used to study split-brain patients -- naturally occurring eye movements can bring information from both visual fields into the two hemispheres.  Moreover, there are other pathways that permit interhemispheric communication, such as the anterior commissure, or the thalamus and other subcortical structures. 

Hemispheric Specialization

Studies of "split-brain" patients, and also of subjects with intact brains, show that there is specialization of function as well as location. For example, the aphasias arise from lesions in the left hemisphere, indicating that speech and language functions are confined to that portion of the brain.

The left hemisphere is specialized for

By contrast, the right hemisphere is specialized for nonverbal functions, including

Hemispheric specialization is not absolute.  The right hemisphere can perform simple functions corresponding to those of the left hemisphere, including language (which is how split-brain patients can respond to directions with their right hemispheres).  Similarly, the left-hemisphere can perform functions that are ordinarily the province of the right hemisphere.  These relations are nicely illustrated by the phenomenon of hemispatial neglect.  As discussed earlier, patients with right-hemisphere damage in the area of the temporo-parietal junction (TPJ) tend to neglect the left side of the spatial environment -- when asked to bisect a horizontal line, for example, they put their mark about a quarter of the way in from the right, as if they do not see the left half of the line.  In some ways, that makes sense, given what we know about contralateral projection: the right hemisphere processes the left visual half-field, while the left hemisphere processes the right.  So far so good, but patients with left-hemisphere damage in the same TPJ area don't generally show neglect of the right.  How could that be?  The classic solution was proposed by Heilman and Valenstein (1979):

• The right hemisphere actually controls attention bilaterally, to both the left and right visual half-fields.
• The left hemisphere controls attention only in the right field.
• Activity in the right hemisphere inhibits activity in the left hemisphere.
• When the right hemisphere is damaged, resulting in neglect of the left visual field, the left hemisphere continues to function, but only processes information in the right field.
• When the left hemisphere is damaged, the right hemisphere continues to function normally, controlling attention in both visual fields.

The situation may be a little more complicated than H&V thought it was -- not least because they didn't take account of later developments in attention theory, notably Posner's distinction between disengaging, shifting, and (re-)engaging attention.  But that's the short version of the story, and you'll learn the longer version if you take a more advanced course in cognitive psychology or cognitive neuroscience.

These specializations are most apparent in a selected sample of the population consisting of right-handed males who have no history of "sinistrality" (left-handedness) in the family. Specialization is not necessarily reversed in sinistrals (left-handers) and females, however (for a discussion of sex differences in lateralization, see Sex and Cognition by Doreen Kimura, 1999). If a person is left-handed, the right hemisphere has better fine motor control. But language is localized in the left hemisphere in both right- and left-handers. As a rule, left-handers and females don't show evidence of strong lateralization, meaning that they enjoy greater flexibility of functioning in each hemisphere. This has implications for the recovery of function, as noted below.

The brain does display some degree of hemispheric specialization -- differences that are sometimes labeled "analytic" (for the left) and "holistic" (for the right).  Unfortunately, these differences have been grossly exaggerated in popular psychology.  Brain-imaging studies show that both hemispheres are activated when subjects are engage in both "analytic" or "holistic" tasks.  When we think, we use the whole brain, not just a piece of it. 

Ontogeny and Phylogeny of Lateralization

Why should mental function be lateralized?

From a developmental point of view, human cerebral lateralization seems to be intimately connected with language capacity. And there's a genetic contribution to handedness. Left-handedness runs in families, and may be associated with a specific gene variant known as LRRTM1.

With respect to the phylogeny of lateralization, or the development of lateralization across species, something like "handedness" occurs in a wide variety of species -- if you define "handedness" as stable, consistent, individual difference in preference for doing things with one side of the body as opposed to the other.  It can be predicted that spatial perception should be favored by the right hemisphere, while communication should favor the left. In some birds, singing is, in fact, lateralized on the left. And in rats, lesions to the right hemisphere diminish exploratory activity. But for non-primates, and especially for non-mammals, evidence of lateralization of function is extremely limited. What about primates, those species that are closest to us on the evolutionary tree?

Among the lesser apes, such as monkeys, cortical mass is evenly divided between the right and left hemispheres. There doesn't seem to be any anatomical difference between the hemispheres. While there is no evidence of a strong specialization for visual patterns, there is evidence of left-hemisphere superiority in the processing of meaningful sounds.

Among the great apes, such as chimpanzees (our closest evolutionary cousin), the left hemisphere has more cortical mass than the right -- anatomical evidence of an emerging difference between the hemispheres. But there is no good evidence of paw preference, analogous to handedness, in any nonhuman species. Individuals may prefer the right paw or the left, but the species divide about 50-50, compared to the 9:1 ratio of right- to left-handers among humans.

Of course, contralateral projection is clearly adaptive: it would be extremely maladaptive if both the left and the right hemisphere controlled the right or left part of the body. Aside from this trivial aspect of lateralization, some theorists have argued that lateralization of function is as old as vertebrate species themselves -- that is to say, about 500 million years old. These theorists have argued that, even very early in vertebrate evolution, the left hemisphere was specialized for controlling well-established patterns of behavior, while the right hemisphere was specialized for detecting and responding to unfamiliar or unexpected events. Human specializations for language (chiefly on the left), a preference for right-handedness (capitalizing on the fine motor control of the left hemisphere that came with speech), and face recognition (chiefly on the right) then built on these primeval specializations. (See "Origins of the Left and Right Brain" by Peter F. MacNeilage et al., Scientific American, July 2009).

With respect to the ontogeny of lateralization, or the development of lateralization within a species, there is evidence of hemispheric specialization from birth. Because the left hemisphere is specialized for language, we might hypothesize that speech perception should be favored by the left hemisphere even in infants; and so it is. Among newborns, even those born prematurely, the left hemisphere is more responsive to speech, while the right hemisphere is more responsive to music. This difference does not increase over the first four years of life, while the child is acquiring language function. Thus, the hemispheric difference precede language ability, and are not caused by the acquisition of language. The human infant is born with a left hemisphere already prepared for eventual language.

This pattern illustrates a contradiction of the principle that ontogeny recapitulates phylogeny -- that the development of a structure or function in the individual mirrors or parallels its evolution across species. Human infants are lateralized from birth, while nonhuman animals aren't well lateralized at all. Thus, there are no orderly parallels between ontogeny and phylogeny.

The Advantage of Lateralization

The fact of two hemispheres makes sense: there is a lot of symmetry and redundancy in the human body. Given the fact that we have two brains, corresponding to the right and left hemisphere, contralateral projection makes sense: if one side of the body is controlled by one side of the brain, that will reduce conflict between them (though it is not clear why projection should be contralateral rather than ipsilateral; this is a clue). Lateralization of speech also reduces conflict: we may have two brains but we only have one mouth. the fact that there is no duplication of the speech apparatus means that the two brains will not be competing for the same output channel.

Handedness enhances the transfer and generalization of motor skills. If the right hand is already good at something, it may be easier for it to become good at other things. For similar reasons, it makes sense to have the receptive and expressive functions of language on the same side of the brain. Finally, we want handedness and speech on the same side, since both require fine motor control.

But why the left as opposed to the right? Note that all species that show a bias show superior development of the left hemisphere. Similarly, there appears always to have been a human bias toward right-handedness: A study of Paleolithic cave paintings made in France and Spain between 10,000 and 35,000 years ago found that 77% of "negative hands" (created by blowing pigment onto a hand placed against a cave wall) were of left hands -- suggesting that prehistoric painters generally held the blowing tube in their right hands (C. Faurie & M. Raymond, "Handedness Frequency over more than Ten Thousand Years", Biology Letters, 09/25/03). Right-handedness predominates, but we don't have the foggiest idea why this should be so. There is no obvious advantage of the left over the right side, per se.

In the final analysis, the question Why the left? illustrates the adaptationist fallacy: the popular assumption that every feature of the human body (and mind) evolved for some purpose. In this Panglossian paradigm (named for Dr. Pangloss, a character in Voltaire's satirical play Candide, who thought that all was for the best in this best of all possible worlds), whatever exists, exists because it is best for the organism. This is not necessarily the case. There is nothing inherently adaptive about having two arms and two legs. We could easily have had four of each. We have two arms and two legs for one reason, and one reason only: We are descended from fish with four fins. If the fish had eight fins, then we would have had four arms and four legs, or some other combination adding up to eight.

Ultimately, all species are descended from a single common ancestor. That organism happened to be biased in favor of the left hemisphere; therefore, so are we. It's as simple as that.

Then why does left-handedness occur at all? That's still a mystery.

But handedness does have consequences (aside from the obvious).  It turns out that people prefer objects that are located on their dominant sides: Right-handed people tend to prefer things that are on the right, lefties prefer things that are on the left (Casasanto, 2009, 2012).  This is a demonstration of what is known as embodied cognition, which is the theory that our experience of the world is grounded in our physical experience of the world -- of our environment and our bodies.  Put another way, our thinking is shaped by our bodies. We'll have more to say about "embodiment" in the lectures on Perception and Emotion.

Left Brain, Right Brain; Top Brain, Bottom Brain; Front Brain, Back Brain?

The distinction between the left and right hemispheres has wormed its way into popular culture, but it may be displaced by other dichotomies.

Stephen Kosslyn, a distinguished cognitive neuroscientist, has proposed that a more important distinction is between the "top" of the brain and the "bottom", the two halves being divided by the lateral fissure -- also known as the Sylvian fissure or the fissure of Sylvius (Kosslyn & Miller, 2013).  The general idea is that the top part of the brain, including the parietal lobe and the superior portion of the frontal lobe, is involved in generating expectations, formulating plans, and monitoring progress as these plans are being carried out.  The "bottom" part of the brain, including the temporal and occipital lobes, and the remaining (inferior) portions of the frontal lobe, organizes sensory signals and interprets and classifies sensory-perceptual information in terms of information stored in memory. 

Of course, like the two hemispheres, these two halves of the brain work together: the bottom half tells us what some event means, and the top half figures out what to do about it.  Still, Kosslyn and Miller argue that there are big individual differences in the balance that between top and bottom, generating four basic cognitive "modes" or styles:

Now, of course, it remains to be seen whether the top-bottom distinction holds up any better than the left-right distinction did.  And the point remains that most mental activities use the entire brain, requiring the integrated activity of lots of different modules. 

Still, you can see where this is going: in the not-too-distant future, we can expect to see yet another distinction proposed, this time between the "front" and the "back" of the brain, as divided by the central sulcus -- also known as the fissure of Rolando -- which separates the frontal lobe from the parietal lobe.  Actually, the future is now.  Recall that among the earliest descriptions of functional specialization divided "association cortex" into an anterior portion specialized for thinking and a posterior portion specialized for perception. 

So, if you really want to go crazy, you've got the makings of a giant classificatory scheme, resulting from crossing two hemispheres with top and bottom, and front and back, yielding a 2x2x2 = 8-fold classification of neurological "types".  That seems to be where the Kosslyn-Miller scheme is going. At the same time, we've learned to be wary of the simple left-right scheme, and there's no reason to think that this one will fare any better than the earlier ones.  Things are likely to be more interesting, and complicated, than that.

Localization of Content and the Search for the Engram

There is considerable evidence for localization of function in the brain. Particular psychological functions seem to be served by specific areas of the brain, and when these areas are damaged, their corresponding psychological functions are impaired or lost. But is there evidence for localization of content as well? That is, are specific pieces of knowledge -- your mental picture of your grandmother, for example, or your knowledge about sports cars -- associated with specific bundles of adjacent neurons that make up the memory?

Competing Views of Neural Representation

The easiest answer is that the every memory is represented by a single neuron, or perhaps a small cluster of neurons, located in a particular part of the brain, and that person memories are no exception to this rule. Thus, the nodes in associative-network models of person memory, like those discussed here, have their neural counterparts in distinct (clusters of neurons).  This was the view taken by Richard Semon, a German biologist who characterized the engram as the "permanent record" of knowledge and experience, "written or engraved on the irritable substance" of neural tissue (Semon 1921, p. 24).  For an excellent account of Semon's work and its relation to modern theories of memory, see Stranger Behind the Engram: Theories of Memory and the Psychology of Science (1982), and Forgotten Ideas, Neglected Pioneers: Richard Semon and the Story of Memory(2001), both by Daniel Schacter, himself a distinguished neuropsychologist who has made important contributions to our understanding of memory and its biological basis.

The Localist View

Although Semon himself was quickly forgotten, Early research by Wilder Penfield (1954), a Canadian neurologist, suggested that engrams actually exist.  In the process of diagnosing and treating cases of epilepsy, Penfield would stimulate various areas of the brain with a small electrical current delivered through a microelectrode implanted in the brain. This procedure does not hurt, because the cortex does not contain afferent neurons, and patients remain awake while it was performed. Accordingly, Penfield asked patients what they experienced when he stimulated them in various places. Sometimes they reported experiencing specific sensory memories, such as an image of a relative or the sound of someone speaking. This finding was controversial: Penfield had no way to check the accuracy of the memories, and it may be that what he stimulated were better described as "images" than as memories of specific events. In any event, the finding suggested that there were specific neural sites, perhaps a cluster of adjacent neurons, representing specific memories in the brain.

Distributed Representations

However, evidence contradicting Penfield's conclusions was provided by Karl Lashley (1950), a neuroscientist who conducted a "search for the engram", or biological memory trace, for his entire career.Lashley's method was to teach an animal a task, ablate some portion of cerebral cortex, and then observe the effects of the lesion on learned task performance. Thus, if performance was impaired when some portion of the brain was lesioned, Lashley could infer that the learning was represented at that brain site. After 30 years of research, Lashley reported that his efforts had been entirely unsuccessful. Brain lesions disrupted performance, of course. But the amount of disruption was proportional to the amount of the cortex destroyed, regardless of the particular location of the lesion.

Lashley's Law of Mass Action states that any specific memory is part of an extensive organization of other memories. Therefore, individual memories are represented by neurons that are distributed widely across the cortex. It is not possible to isolate particular memories in particular bundles of neurons, so it is not possible to destroy memories by specific lesions.

At about the same time, D.O. Hebb, a pioneering neuroscientist, argued that memories were represented by reverberating patterns of neural activity distributed widely over cerebral cortex. Hebb's suggestion was taken up by others, like Karl Pribram, another neuroscientific pioneer, who postulated that memory was represented by a hologram, in which information about the whole object was represented in each of its parts.

Connectionist models are inspired, in part, by both Lashley's Law of Mass action and Hebb's reverberating-network model of memory.

Locationism Revived

Despite the power of Lashley's data (not to mention his reputation as the leading physiological psychologist of his day), Penfield's vision held some attraction for some neuroscientists, who continued to insist that individual memories were represented by the activity of single neurons, or at most small clusters of neurons, at specific locations in cortex.

Problems with Penfield's clinical studies aside, early advances in understanding the neural basis of perception led support to the localist views of representation.

While these neural systems responded to the physical properties of the stimulus, their discovery fed speculation that the meaning of the stimulus, and other cognitive contents, might similarly be represented by a localized cluster of neurons.

Nobody, including Lettvin and Barlow themselves, took any of this all that seriously, and neuroscientific doctrine has emphasized distributed representations of the sort envisioned by Lashley and Hebb -- until recently, that is.

Xu Liu, Susumu Tonegawa, and their colleagues (2013) may actually have succeeded where Lashley failed, by looking in a different place -- the hippocampus, rather than the cerebral cortex.  It has been known at least since H.M. that the hippocampus is critical for memory.  But it is also known as a cognitive map -- a representation of the location of objects in space (the term was introduced by Tolman on the basis of his work on latent learning of mazes, which we'll discuss in the lectures on Learning).  O'Keeffe and Nadel (1978) found place cells in the hippocampus that become activated when the organism (usually, a rat) visits a particular location.  when an animal learns its way through a maze, a particular pattern of cells, apparently corresponding to the pathway, is activated in the hippocampus.  And, interestingly, that same pattern of activation is "replayed" while the rat sleeps, apparently aiding consolidation of the memory (Wilson & McNaughton, 1994). Liu et al. allowed rats to learn a particular environment, and identified the cells in the hippocampus that represented what they had learned.  The next day, in a different environment, they reactivated those cells at the same times as they delivered a foot shock to the animal.  On the third day, they placed the animal in the first environment (i.e., from Day 1), and observed that the rats froze, a behavioral manifestation of fear.  So, Liu et al. seem to have discovered Semon's engram -- a specific group of neurons that represent something that the organism has learned.

On the other hand, the hippocampus is a highly specialized structure -- specialized for cognitive mapping.  And rats are very specialized creatures -- they're really good at learning and remembering places.  It may well be that engrams for spatial knowledge are represented locally, as discrete groups of neurons, while engrams for other kinds of knowledge -- the articles of the Bill of Rights, for example, or the names of your immediate family members, or what you did last Thursday -- may be represented in a more distributed fashion. 

Except....

A "Halle Berry" Neuron?

A serendipitous finding, ingeniously pursued by a group of investigators at UCLA and Cal Tech, also suggests that there might be something to the idea of a "grandmother neuron" after all (Quian Quiroga, Reddy, Kreiman, Koch, & Fried, Nature, Vol. 425, pp. 1102-1107, June 23, 2005; see also "Brain Cells for Grandmother" by Quian Quiroga, Fried, & Koch, Scientific American, 02/2013).

These investigators worked with eight patients with intractable epilepsy. In order to localize the source of the patients' seizures, they microelectrodes in various portions of the patients' medial temporal lobes (the hippocampus, amygdala, entorhinal cortex, and parahippocampal cortex. Each microelectrode consisted of 8 active leads and a reference lead. They then recorded responses from each lead to visual stimulation -- pictures of people, objects, animals, and landmarks selected on the basis of pre-experimental interviews with the patients.

In one patient, the investigators identified a single unit (i.e., a single lead of a single electrode, corresponding either to a single neuron or to a very small, dense cluster of neurons, corresponding to only a single active lead), located in the left posterior hippocampus, that responded to a picture of the Jennifer Aniston, an actress who starred in a popular television series, Friends. (A response was defined very conservatively as an activity spike of magnitude greater than 5 standard deviations above baseline, consistently occurring within 1 second of stimulus presentation). That unit did not respond to any other stimuli tested. The investigators quickly located other pictures of Aniston, including pictures of her with Brad Pitt, to which she was once (and famously) married. The same unit responded to all the pictures of the actress -- except those in which she was pictured with Pitt!

Similarly, a single unit in the right anterior hippocampus of another patient responded consistently and specifically to pictures of another actress, Halle Berry (who in won an Academy Award for her starring role in Monsters' Ball). Interestingly, this unit also responded to a line-drawing of Berry, to a picture of Berry dressed as Catwoman (for her starring role in the unfortunate film of the same name), and even to the spelling of her name, H-A-L-L-E--B-E-R-R-Y (unfortunately, the investigators didn't think of doing this when they were working with the "Jennifer Aniston" patient -- remember, they were flying by the seat of their pants, doing this research under the time constraints of a clinical assessment). The fact that the unit responded to Berry's name, as well as to her picture, and to pictures of Berry in her (in)famous role as Catwoman, suggests that the unit represents the abstract concept of "Halle Berry", not merely some configuration of physical stimuli.

As another example, yet a third patient revealed a multi-unit (i.e., two or more leads of a single electrode, evidently corresponding to a somewhat larger cluster of neurons) in the left anterior hippocampus that responded specifically, if not quite as distinctively, to pictures of the Sydney Opera House. This same unit also responded to the letter string SYDNEY OPERA HOUSE. It also responded to a picture of the Baha'i Temple -- but then again, in preliminary testing this patient had misidentified the Temple as the Opera House! So again, as with the Halle Berry neuron, the multi-unit is responding to the abstract concept of the Sydney Opera House", not to any particular configuration of physical features.

Across the 8 patients, Quian Quiroga et al. tested 993 units, 343 single units and 650 multi-units, and found 132 units (14%) that responded to 1 or more test pictures. When they found a responsive unit, they then tested it with 3 to 8 variants of the test pictures. A total of 51 of these 132 units yielded evidence of an invariant representation of people, landmarks, animals, or food items. In each case, the invariant representation was abstract, in that the unit responded to different views of the object, to line drawings as well as photographs, and to names as well as pictures.

Research by UCB's Jack Gallant and his colleagues has also provided evidence for a sort of localization of knowledge.  I have already discussed Gallant's astounding research on visual perception, in which they showed that specific scenes were associated with specific patterns of brain activation in the visual cortex -- so specific that they were able to predict, from the pattern of brain activity, what images their subjects were viewing.  In further research, they turned their attention to the representation of specific concepts (Huth et al., Nature 2016).  Using fMRI, they recorded activity over the entire cerebral cortex (about 50,000 voxels) for two hours while subjects listened to stories presented on The Moth Radio Hour series on public radio.  They first analyzed the co-occurrences between each word used in the stories (over 10,000 of them)and other words in the English language, to identify a small number of semantic domains.  For example, one domain related to humans, society, and emotions; another consisted of concrete terms, and yet another consisted of abstract terms.  The image on the left shows, at the top, various semantic domains.  In the middle is a "flattened" view of the cerebral cortex.  At the bottom are the more familiar lateral and medial views of the cortex.  The image on the right illustrates what the "dictionary in the brain" of one subject looks like.

• Every word activated a widely distributed area of the brain, consistent with the Law of Mass action. 
  
• At the same time, each word had a "center" of high activation, consistent with the Doctrine of Localization. 
  
• Semantically related words activated the same general regions of the brain.
• Most surprisingly, there were strong commonalities across the subjects tested: they weren't identical, but there were striking similarities.
  

The result of this research is a sort of "atlas" of where different concepts are represented in the brain.  That is, in the brain of a single individual subject.  Othere subjects show different patterns of activation to the same concepts.  But the point is that, when the same subject is tested repeatedly with a word, the same pattern of activation is observed.

So maybe there are "grandmother neurons" after all!  Quian Quiroga's research -- which, remember, was performed in a clinical context and thus may have lacked some desirable controls -- identified sparse neural representations of particular people (landmarks, etc.), in which only a very small number of hippocampal units is active during stimulus presentation. Huth and Gallant's research showed identified similar sparse representations for particular semantic concepts in the cerebral cortex.

Of course, this evidence for localization of content contradicts the distributionist assumptions that have guided cognitive neuroscience for 50 years. Further research is obviously required to straighten this out, but maybe there's no contradiction between distributionist and locationist views after all. After all, according to Barlow's (1972) psychophysical linking principle,

Whenever two stimuli can be distinguished reliably... the physiological messages they cause in some single neuron would enable them to be distinguished with equal or greater reliability.

In other words, even in a distributed memory representation, there has to be some neuron that responds invariantly to various representations of the same concept. Neural representations of knowledge may be distributed widely over cortex, but these neural nets may come together in single units.And it makes sense that the invariant neurons associated with some concept are located near to invariant neurons associated with semantically related concepts. 

Speaking Through the Brain Gallant's research, and other work like it, is not just of theoretical significance: it also has potential practical importance.  Consider a case study recently reported by Edward Chang, a neurosurgeon at UCSF (NEJM, 2021; see "Brain Signals 'Speak' for Person with Paralysis" by Kelly Servick, Science, 07/16/2021).  A patient had suffered a massive stroke that rendered him quadriplegic (paralyzed from the neck down) and anarthric (unable to control his speech musculature).  He was otherwise conscious, though, and communicated by spelling out words letter-by-letter using movements of the head.  This is the usual mode of communication for such patients, but it is very cumbersome: using this traditional method the patient was able to produce only about five words per minute.  In an experimental attempt to make communication more efficient, Chang et al. laid a sheet of electrodes over the patients exposed motor cortex (including Broca's area) and recorded brain activity when he attempted to speak particular words.  Using a machine-learning algorithm, the computer then acquired a "vocabulary" of about 50 common words.  This was possible because, even though the patient could not actually speak, he could try to speak, or imagine speaking, even though the signals could never reach his vocal apparatus.  Then the procedure was repeated with simple sentences composed of that vocabulary, such as "Bring my glasses, please".  Eventually, the algorithm achieved an error rate of only 25%, compared to a rate of 92% expected on the basis of chance.  With this new technique, the patient was able to improve his "speech" rate to about 18 words per minute. This level of performance was all the more remarkable because the patient had been in this condition for more than 10 years, affording plenty of time for his motor cortex to reorganize itself to accommodate the absence of speech signals.

Recovery of Function

It has been generally thought that, once a part of the central nervous system has been damaged through injury, insult, or disease, the function served by the lesioned area is lost forever. This is because central nervous system tissue does not repair itself. However, there are some cases of recovery of function, and they represent an interesting challenge to our theories of the brain.

But recovery of function is by no means guaranteed. Christopher Reeve, the actor who starred in the Superman series of films, was in an equestrian accident in 1995 which severed his spinal cord very high up, between the first and second vertebrae, resulting in quadriplegia. Despite an extremely vigorous and expensive rehabilitation regime, he was confined to a wheelchair, and breathed only with the aid of a respirator, until he died in 2004.

In some cases, recovery occurs simply because the damage is incomplete, and enough tissue has been spared that some function can be regained. For example, Gregoire Courtine and his colleagues (2012) paralyzed the hind legs of rats by severing all direct connections from the spinal cord to the hind legs, without severing their spinal cords incompletely -- simulating the sort of injury that occurs in as many as one-third of paraplegic patients. Initially, the rats were unable to walk -- reasonably enough, as motor signals from the brain could not be transmitted through the affected spinal nerves to the hind-leg muscles. But over an extended period of physical rehabilitation, in which the animals were supported in a harness and then given a food reward for moving themselves forward, they were able to regain a fair amount of control over their hind limbs. It was apparently critical to this process that, in addition to the harness and the food, the animals received injections of serotonin and dopamine in the damaged area, as well as electrical stimulation in the brain, and in the spinal cord itself. Analysis of the spinal-cord tissue revealed an increase in density of nerve fibers running from the brain, down the spinal cord, past the damaged area and out to the legs.

But there are also some more interesting possibilities.

Redundancy in Neural Organization

In other cases, the recovery occurs because of redundancy in neural organization. For example, the ventral hypothalamus may be primarily responsible for regulating eating behavior, and Broca's area responsible for fluent speech, but some other center may also be able to take on this responsibility, if the primary center is damaged. For example, recovery from aphasia is more likely in children, who have immature nervous systems, and in fact there are cases where a very young child sustained damage in the left-hemisphere speech areas, and grew up to have speech localized in the right hemisphere. Recovery is also more likely in left-handers and females, whose brains are less rigidly organized than right-handed males. These outcomes suggest that the right hemisphere may also contain speech and language centers that go unused under ordinary circumstances. According to one theory, activity of the redundant module is suppressed by the activity of the primary module; when the primary module is destroyed, the redundant one is disinhibited, and begins to take over the function in question. 

Neurogenesis

Recent advances in scientific knowledge raise yet another possibility: that recovery of function can be mediated by the growth of new neural tissue -- a controversial phenomenon known as neurogenesis. The traditional doctrine within neuroscience, formulated by Prof. Pasko Rakic of Yale University, has been that an organism is born with all the neurons that it will ever have, and that neural loss is, to all intents and purposes, permanent -- especially so far as the central nervous system is concerned. If so, the functions lost through brain lesions can never be regained.

However, evidence for neurogenesis has steadily accumulated over the years. Prof. Fernando Nottebohm of Rockefeller University found it in some species of adult songbirds, and suggested that neurogenesis was necessary to enable the birds to learn new songs. In addition, early work performed independently by Joseph Altman and by Michael Kaplan found evidence of neurogenesis in mammalian species. More recently, Elizabeth Gould, working first at Rockefeller and then at Princeton University, found evidence of neurogenesis in the hippocampus of rats, marmosets monkeys, and macaque monkeys. Her findings have now been confirmed by Rakic himself, and by Prof. Fred Gage of the Salk Institute (Gage is actually a descendant of Phineas Gage, a famous 19th-century neurological case). In 1999, Gould reported neurogenesis in the neocortex (not just in subcortical structures like the hippocampus or the olfactory bulb) of macaque monkeys (Science, 286, 548f).

Why has evidence of neurogenesis not been forthcoming until now? One reason is social and political in nature: the doctrine that the organism is born with all the neurons it will ever have, and that neurons can only die, not be born, has been so powerful in neuroscience that most people simply accepted it as true. But, to be fair, it is only recently that new techniques have enabled investigators like Gould to perform really convincing studies demonstrating neurogenesis. In addition, the laboratory animals used in the older studies were kept, as was common at the time, in somewhat deprived living conditions. Gould argues that new neurons are born all the time, but that they only live when the environment is rich and challenging, providing the organism with things to do and learn.The more complicated the learning task, the more neurogenesis occurs, and the longer the new neurons last.

The debate continues. In 2001, Rakic reported that he could not replicate Gould's finding of neurogenesis in macaque neocortex (Science, 294, 2127-2131). New neural cells were formed, but only in the hippocampus and olfactory bulb, not the cerebral cortex. New cells were formed in the cortex, too, but inspection with a special microscope indicated that they were not neurons. Instead, the new cortical cells were of other types, such as glia cells, which are also found in neural tissue. Gould, Rakic claims, mistakenly identified these cells as neurons. Gould, for her part, asserts that she found neurons as well as non-neuronal cells, and suggests that Rakic's technique was not sufficiently sensitive to see what she saw.  Still, in 2013, researchers using a form of radiocarbon dating failed to detect any evidence of neurogenesis in the olfactory lobe, cerebellum, or neocortex.  This study left the claim of neurogenesis in the hippocampus intact.

The story continued in 2018, with two different research groups reporting, almost simultaneously, contradictory findings employing a new immunosassay technique with post-mortem brain specimens to detect proteins commonly found in new neurons.  Consistent with the classic doctrine, the first study found lots of the proteins in fetal and infant brains, but very little after 1 year of age (Alverez-Buylla & Sorrells, Nature, 2018).  However, the second study, which obtained its specimens more quickly after the individuals' deaths, detected the proteins even in the brains of people in their late 70s (Boldrini et al., Cell, 2018).  The proteins in question are known to break down quickly after death, so it is possible that that the timing of the first study was unfortunate.  It is also possible that, while neurogenesis can occur in adults, it is more likely to occur in infants and other young children.  Yet a third study, by Maria Llorens-Martin et al. (Nature Medicine, 2019) discovered that the evidence for neurogenesis depended to some degree on the precise manner in which the brains had been preserved; and that there was more evidence of neurogenesis in individuals who had died before they showed signs of neurocognitive impairment, compared to those who had died with Alzheimer's disease or other neurodegenerative disease.

Note that all three groups focused on the hippocampus, so even if Boldrini and Llorens-Martin are right, the matter of neurogenesis in neocortex remains unresolved.

An authoritative review of this research by Fred Gage, a prominent neuroscientist (and, perhaps, distant relative of the famous neurological patient Phineas Gage) concludes that, while neurogenesis pretty definitely occurs in the hippocampus, but probably not in the neocortex, cerebellum, or olfactory bulb (Science, 05/31/2019).  Gage points out that neurogenesis occurs in several phases, meaning that we need just the right combination of conditions to have neurogenesis occur at all.  Physical activity (running) facilitates the proliferation of neural progenitor cells, while learning, and especially stress, inhibits it; learning promotes the differentiation of progenitor cells into neurons; learning, together with environmental enrichment, promotes the survival of the new neurons.  Neurogenesis in hippocampus wouldn't allow Christopher Reeve to walk again, but it probably does play an important role in memory.

Stay tuned for further developments! 

If Gould is proved to be right, her research suggests that that the brain does actually produce new neurons to replace those that die naturally during the lifespan. Moreover, research by Gage suggests that stem-cell transplantation may make it possible to regenerate neural tissue.If this technique is going to work, the secret is not likely to be in the surgical details of the transplantation technique. Rather, the new tissue is going to have to be stimulated to grow and make connections to each other and to pre-existing brain tissue.

For an engaging account of these recent scientific discoveries, see:

This new research raises the possibility that lost functions can be restored, at least to some degree, by stimulating the growth of new neurons, and directing them to sites where they can take over lost functions. Experimental treatments for Parkinson's Disease follow this model. It is the prospect of such cures, among others, that makes research on embryonic stem cells so exciting. However, this research is at a very early stage, and it is very controversial. Don't expect major cures for CNS damage in your lifetime: protect your CNS at all times! Use that seat belt, wear that bicycle helmet, and don't dive into shallow or unfamiliar water.

Plasticity

Recovery can also be mediated by the plasticity of the nervous system. It turns out that the functional organization of the nervous system is not fixed for all time, but can change depending on the organism's circumstances. For example, when people become deaf or blind, their corresponding sensory projection areas don't simply atrophy. Instead, it seems that they can be co-opted by other sensory functions.

Plasticity can be observed in classic experiments by Merzenich, Kass, and others. Recall the motor and somatosensory areas of the frontal and parietal lobes, respectively. These areas show a somatotopic cortical mapping such that -- to take the example of the somatosensory area -- the part of the parietal lobe that processes tactile sensation from the hand is next to that which processes tactile sensation from the arm, and the part that processes tactile sensation from the foot is next to that which processes tactile sensation from the leg, etc. This one-to-one or point-to-point mapping is depicted in the motor and somatosensory homunculus, and it is very detailed, such that the area for the index finger is adjacent to the area for the middle finger, which in turn is adjacent to the area for the ring finger, etc.

Here’s a famous example of plasticity in the hippocampus.  You’ll remember, from an earlier lecture, that the hippocampus plays an important role in memory.  This is especially true with respect to memory for spatial location, and the 2014 Nobel Prize in Physiology or Medicine was given to a group of scientists who showed that the posterior portion of the hippocampus is composed of “place cells” that fire whenever an organism is in a particular place in the environment, and which constitute a kind of “cognitive map”.  Now in order to be licensed to drive a taxicab in London, drivers must learn how to navigate among thousands of different locations in the city – what is known in the trade as “The Knowledge”.  A brain-imaging study of a group of London taxi drivers showed a redistribution of gray matter in the hippocampus: reduced volume in the anterior portion, and increased volume in the posterior portion, compared to a control group (Maguire et al., 2000).  Further, this change was correlated with the subject’s experience as a cab driver.  Apparently learning a detailed map of London, and perfecting this “Knowledge” by actually driving on the streets day in and day out, causes structural change in the hippocampus. 

Along the same lines, Meschelli et al. (2004) found that English-Italian bilinguals showed increased gray-matter density in the left inferior portion of the parietal lobe, compared to English monolinguals.  This area is activated when subjects perform tasks requiring verbal fluency.  The earlier the subjects had learned Italian, and the more proficient they were in their second language, the bigger the difference in brain density.

One illustration of neural plasticity may be phantom limb sensations  Many patients who have undergone the surgical amputation of a limb often report that they continue to feel sensations, including pain, emanating from that limb -- even though they know it's it's not there anymore.  They may also experience the phantom limb as moving.  For a long time, surgeons believed that phantom limb pain emanated from swollen nerve endings in the remaining stump of the limb, which they tried to treat by pruning the stump further away -- even going so far as to sever the nerves where they joined the spinal cord.  This didn't work, leading the surgeons to conclude that the pain was "all in the head", reflecting poor psychological adjustment to the amputation.  One prominent theory, initially proposed by Melzack (1989) and promoted by Pons et al. (1991) and Ramachandran et al. (1998; Ramachandran & Blakeslee, 1998) is that phantom limbs are actually a consequence of neural plasticity.  For example, the region of somatosensory cortex which originally coded for the amputated limb will no longer receive somatosensory stimulation from that body part, and may become attached to surrounding cortex; sensations processed by this area are then referred to the amputated limb. So, for example, sensations of touch to the face might be referred to an amputated hand.

Similar experiments have been performed on the auditory area in the temporal cortex, which shows a tonotopic mapping, such that close frequencies are processed by adjacent areas: the area that processes a tone of 500 hertz (cycles per second) is adjacent to the one that processes a tone of 450 hertz. If an organism is given extensive practice in discriminating between two tones, the areas of the auditory cortex that process those tones become larger.

And similarly, the visual area of the occipital cortex is characterized by retinotopic mapping, such that adjacent areas of the retina project to adjacent areas of the occipital cortex. If a lesion is made in a particular area of the retina, so that its corresponding visual area no longer receives stimulation from that area, this area will expand into adjacent areas of the retina.

A famous example of plasticity occurs in the hippocampus.  You’ll remember, from an earlier lecture, that the hippocampus plays an important role in memory.  This is especially true with respect to memory for spatial location, and the 2014 Nobel Prize in Physiology or Medicine was given to a group of scientists who showed that the posterior portion of the hippocampus is composed of “place cells” that fire whenever an organism is in a particular place in the environment, and constitute a kind of “cognitive map”.  Now in order to be licensed to drive a taxicab in London, drivers must learn how to navigate among thousands of different locations in the city – what is known in the trade as “The Knowledge”.  A brain imaging study of a group of London taxi drivers showed a redistribution of gray matter in the hippocampus: reduced volume in the anterior portion, and increased volume in the posterior portion, compared to a control group.  Further, this change was correlated with the subject’s experience as a cab driver.  Apparently learning a detailed map of London, and perfecting this “Knowledge” by actually driving on the streets day in and day out, causes structural change in the hippocampus.

Neural plasticity is involved in the acquisition and exercise of new skills, which may involve not just changes in the synaptic connections among existing neurons, but also the generation of entirely new ones. Many examples come from professional, semi-professional, and student musicians Jancke, 2009):

In addition to a surplus of glia cells, the posterior portion of Einstein's parietal lobes had larger gyri than average, implying a greater density of neurons. This difference has been linked to Einstein's use of mental imagery in thinking -- for example, the "train thought experiment" by which he propounded his theory of relativity. But in this case, we don't know which came first: the neural chicken or the imagistic egg.

Specialization versus Holism

Taken together, the literature on recovery of function and the Law of Mass Action set limits on the nature of functional specializations in the brain, because it implies that every part of the brain is involved in "higher" mental functions.

An excellent example of this point comes from a study by UCB's Jack Gallant and his colleagues (2013).  They asked subjects to watch a very long sequence of video clips, each of which included a living (cat or plant) or nonliving (clock or building) object.  Some subjects were asked to indicate whether each clip contained a person or a vehicle. While they were performing this task, their brain activity was recorded using fMRI.  Using special software, the brain was divided into a three-dimensional grid, and the activity in each segment of the grid, known as a voxel, was recorded every second that the subjects were watching the video. 

It was as if the entire brain was being "retuned", depending on the task, to pick up both the attended category (people or vehicles) and semantically related objects (plants and cats, or clocks and buildings).  

The full story of cortical function is a blend of specialization and holism. There is no question that particular parts of the brain are specialized for particular mental functions. But the brain is not just a bunch of pieces, each operating independently of the others to perform some narrow function. On the contrary, evidence for the holistic organization of the brain is found by the fact that most functions are performed by "systems" or "circuits" involving several different brain modules. Also, the contents of the knowledge store are distributed widely across the cortex.

In the immature brain, there appears to be considerable equipotentiality, which means that several different areas are able to carry out a particular function. Functional specialization becomes solidified as the brain matures. In cases of severe damage, some degree of plasticity in the brain means that other modules may have the potential for taking over the lost function -- especially in a brain that is immature or not rigidly organized. But each site in the brain appears to be pre-ordained for a particular function. If a module should take on a new function, it may lose the capacity to perform its own specialty, or it may not be able to perform either the new or the old function optimally.

Performance of most mental and behavioral tasks requires the integration and coordination of many different brain modules. the brain operates as a whole, not as a collection of independent pieces. But each module makes its own contribution to the functioning of the whole.

Still, the implication of the modularity argument is that the brain is a "mental toolbox" whose various implements -- the various mental modules and their corresponding brain systems -- evolved to help humans meet the demands posed by what evolutionary psychologists call the Environment of Early Adaptation (EEA) -- basically, the East African savanna of the Pleistocene Era, which began bout 1.8 million years ago.

That is all well and good, and one could argue that this mental toolbox has served us well -- and, on the other side of the coin, it seems possible that some of the errors we make in thinking (about which there is more in the Lecture Supplement on Thought and Language) reflect the fact that evolution has not had time to catch up with the fact that we now navigate in a quite different environment than the EEA.

On the other hand, it also seems at least equally likely, if not more so, that there is more to mental life than a collection of highly specialized mental tools. After all, we humans did not confine ourselves to the East African savanna. Very quickly we began to migrate out of that environment:

More recently, of course, we have established more-or-less permanent outposts in extremely inhospitable environments of Antarctica and outer space.

For such migrations to take place, we had to be able to draw upon more than a set of highly specialized mental tools, geared to the demands of a specific time and place. We also needed a capacity for general intelligence, enabling us to solve the problems posed by the new environments into which we migrated -- or, to be more blunt about it, adapt our new environments to us. We also needed a capacity for learning, allowing us to acquire new knowledge, and new mental tools, at a much faster place than biological evolution allows.

It is to this capacity for learning that we turn next.

This page last revised 04/26/2023.