SOMs are pieces of fictions in the disguise of autobiography

What is the case, though, is that the senses, the nervous systems, and the behaviors of each animal began to evolve in response to the senses, nervous systems, and behaviors of others. The actions of one animal created opportunities for and demands on others. If a yard-

The Cambrian witnessed the appearance of both the compound eyes seen today in insects and camera eyes like our own.

these animals.

only three of the major animal groups produced some species with complex active bodies (CABs). Those groups are arthropods, chordates (animals like us with a nerve cord down their back), and one group of mollusks, the cephalopods.

anomalocarid.

What an amazing image: in a long evolutionary process, a motion-controlling brain marches up through your head to meet there some light-sensitive organs, which become eyes.

When we try to compare one animal’s brainpower with another’s, we also run into the fact that there is no single scale on which intelligence can be sensibly measured.

panpsychists

tactile vision substitution systems (TVSS),

The story I am working toward is one of gradual change: as sensing, acting, and remembering became more elaborate, the feel of experience became more complex along the

The senses can do their basic work, and actions can be produced, with all this happening “in silence” as far as the organism’s experience is concerned. Then, at some stage in evolution, extra capacities appear that do give rise to subjective experience: the sensory streams are brought together, an “internal model” of the world arises, and there’s a recognition of time and self.

These results do provide support for a view of pain as a basic and widespread form of subjective experience, one present in animals with very different brains from ours.

try. The title of this chapter

Subjective experience does not arise from the mere running of the system, but from the modulation of its state, from registering things that matter. These need not be external events; they might arise internally. But they are tracked because they matter and require a response. Sentience has some point to it. It’s not just a bathing in living activity.

deimatic

These sensations

The nervous system arose through one internalization of sensing and signaling, and the internalization of language as a tool for thinking was another.

Diaries and notes-to-self are embedded in a sender/ receiver system, just like more standard kinds of communication.

Cells can generate the right arrangement when a person is conceived, born, and develops from a baby to an adult. Why can’t the arrangement needed to keep you alive be constantly regenerated by the newly arriving cells?

The evolutionary theory of aging gives us an explanation for the basic facts of age-related decay. It explains why breakdown starts to appear in old individuals as if on a schedule.

Neuroplasticity—

the unfathomable complexity of living systems places substantial limits on any sort of seemingly simple explanation.

conspecific.

is our

The ability to create and deploy powerful weapons, a result of our sophisticated intelligence and ability to understand the world through physical and mathematical reasoning, has formed a deadly marriage with our primal capacity for fear and violence.

will adopt the following definition of mind: the collection of mental experiences.

By mental experiences I mean our subjective (first-person, internal) experiences, including our thoughts, feelings, perceptions (visual, auditory, olfactory, gustatory, tactile), mental images, and sense of self. The term consciousness is often also used

This is the task in psychoanalysis: bringing unconscious things related to one’s behavior into consciousness, into awareness, where they can be subjected to analysis and become amenable to change.

Kunstformen der Natur (Artforms of Nature) by Ernst Haeckel.

Drosophila

diencephalon,

Andreas Vesalius (1514–1564), a physician who lived and taught in Italy. His book was called De Humani Corporis Fabrica, which translates as On the Fabric of the Human Body, and was spectacularly illustrated

Figure 2.9. Open human skull with dura intact (left) and with dura peeled back (right), from Andreas Vesalius’s De Humani Corporis Fabrica (1543).

“I sing the body electric.”

One of the beautiful things about the periodic table of chemical elements is that an atom’s position on the table tells us whether it is likely to give up electrons and become a positively charged ion (called a cation) or take on electrons and become a negatively charged ion (called an anion). Elements on the far left side of table will easily give up electrons

they form a collection of unreactive gaseous elements called the noble or inert gases.

This sharing of electrons between atoms is called a covalent chemical bond.

the United States, fluoxetine is associated with the brand name Prozac.

Largely from these four elements—carbon, hydrogen, oxygen, and nitrogen—are built the basic structures of an enormous number of biologically interesting molecules.

Organic molecules composed solely of carbon and hydrogen are called hydrocarbons.

double bond,

(polymers)

While not the most abundant neurotransmitters in the human brain,

So the oxygen atom in water becomes slightly negatively charged and the hydrogen atoms in water become slightly positively charged. This is what is meant by polarity. Polar means separation, and in this case there is a separation of charge between different parts of the water molecule. Water is a polar molecule.

hydrogen bonding—the slightly negative oxygen atom of one water molecule is attracted to the slightly positive hydrogen atom of another.

In the absence of water, NaCl is an extremely stable structure. However, introduce even a small amount of water and the NaCl will begin to dissolve, that is, fall apart into the water.

Below four fundamental types of biological molecules are described: lipids, proteins, carbohydrates, and nucleic acids.

Lipophilic (lipid loving) is synonymous with hydrophobic. And conversely, lipophobic (lipid fearing) means the same as hydrophilic. Oil and water don’t mix.

phospholipids.

phosphatidylcholines,

This configuration is called a quaternary amine.

Indeed, phospholipid bilayers constitute the membranes forming the boundary layers around all cells for all of life on Earth.

many ways, these membranes are more like fluids in their properties than they are like solids.

So, first, what is an amino acid? In organic chemistry, an amino acid is a molecule that contains both an amine group (–NH2) and a carboxylic acid group (–COOH). The amino acids used as protein building blocks

these are termed alpha-amino acids. Here R represents a portion of the molecule

polypeptide.

Ribosomes

cell. Any chain of amino acids is called a polypeptide; if it is more than about forty amino acids long, then it is called a protein. The threshold number for defining when a polypeptide becomes a protein is somewhat arbitrary. Some might say thirty, some fifty.

lipids, proteins, carbohydrates, and nucleic acids.

backstory.

soma,

It is analogous to a crowd of thousands of people doing a wave at a sport event.

action potential

axon hillock

Cholesterol is an important component in all lipid bilayer membranes in animals, contributing to the structural integrity and the fluidity

components of the neuronal cytoskeleton (see Chapter 10).

Insects don’t have myelin, and there are no giant insects in part because it would be difficult to coordinate the synchronous movement of muscles in a large body using more slowly conducting unmyelinated nerves.

Synapses come in two varieties: electrical and chemical.

a gap junction)

When the term synapse is used without further qualification, it generally refers to a chemical synapse.

SNARE complex,

calcium binds to proteins present in the SNARE complex, and a sequence of molecular events results in fusion of the vesicular membrane with the boundary membrane of the axon terminal. The contents of the storage vesicle—the neurotransmitter molecules—then spill into the synaptic cleft. Neurotransmitter release has occurred.

If the appropriate neurotransmitter molecule makes contact with the appropriate receptor protein, it sticks, or binds, like a key in a lock.

These processes of inactivation—either reuptake or enzymatic—act very rapidly and efficiently to remove neurotransmitters from the synapse.

Vagusstoff was later identified to be acetylcholine, the first molecule recognized as a neurotransmitter.

ionotropic receptor.

The most abundant neurotransmitter molecule in the human brain is glutamic acid, or glutamate.

glutamatergic

change in membrane potential—most often by way of ionotropic GABA receptors—is called an inhibitory postsynaptic potential, or IPSP. Just

To recap:

ionotropic

metabotropic

Here is one summary; consider reading through it as you might a poem on first reading—don’t get caught up in the details . . .

Ionotropic receptors

Metabotropic receptors

metabotropic receptors are generally referred to as G-protein-coupled receptors, or GPCRs.

Highlighting again the poetic molecular beauty of all this, here is a sonnet, in Shakespearean form—a lyric poem to the GPCR:

And beyond this, the nervous system is in intimate interaction with the endocrine system, the cardiovascular system, the immune system, and so forth—

The word ganglion (plural ganglia) refers to a cluster of nerve cells.

When the sympathetic nerve fibers make connections

with target tissues—such as the heart, lungs, intestines, bladder, or iris of the eye—the signaling molecule (neurotransmitter) used at those connections is norepinephrine.

An agonist is a molecule that binds to a neurotransmitter receptor and activates it.

the key-and-lock analogy for a neurotransmitter and its receptor, an agonist is like a second type of key that opens the same lock.

An antagonist is a molecule that binds to a neurotransmitter receptor and blocks the action of the neurotransmitter at the receptor.

the key-and-lock analogy, an antagonist is like a key that fits into the lock but doesn’t open

sympathomimetic

parasympatholytic

Unlike glutamate and GABA, molecules that are released by billions of neurons as neurotransmitters, acetylcholine is produced and released by a relatively small number of neurons—perhaps a few hundred thousand—clustered into several regions deep in the brain’s interior.

molecular precursors

group of neurotransmitters in the human brain are the monoamines,

dopaminergic

dopaminergic brainstem nuclei include the substantia nigra and ventral tegmentum

The function of melanin in brain cells (sometimes called neuromelanin) is unknown.

neurotransmitters in the human brain may be grouped into several categories.

All the known dopamine,

receptors are GPCRs.

That a weird molecule like TTX is found in a number of unrelated animal species suggests it is not synthesized directly by the animals themselves but, rather, may be the product of a microorganism living inside these various animals.

There, cells forming the walls of the blood vessels are tightly joined together, with no gaps, no pores, no holes between the cells.

Local anesthetics provide yet another example of the effects of altering sodium channels.

Several synthetic chemicals have been developed that also act as local anesthetics to numb sensation but do not possess the other CNS and autonomic nervous system effects of cocaine.

This results in a reduction

in signals from neurons sending sensory information to the brain—the local anesthetic effect.

The molecular structure diagrams of these drugs remind us that all these chemicals are composed of carbon, nitrogen, oxygen, and hydrogen atoms, hooked together by covalent chemical bonds into specific geometric shapes. The different shapes of the molecules confer upon them their differing pharmacologic properties.

The Latin genus for the plant comes from one of the goddess sisters of Greek myth called the Moirai (plural of Greek moira = share, apportion, fate). These sisters are Clotho, who spins the thread of life; Lachesis, who measures out the thread of life; and Atropos, who cuts the thread of life. In English they are called the Fates.

The history of drugs is mostly a history of ethnobotany,

So pervasive is caffeine consumption that we have, to large extent, lost touch with what a powerful stimulant it is.

barbiturates,

These diverse sedative-hypnotic drugs are all thought to have similar primary neurochemical mechanisms of action in the brain.

About a dozen such molecules have now been identified from animals, collectively called endorphins, a word derived from “endogenous” and “morphine.”

These endogenous opioid neurotransmitters were the first of a new class of neurotransmitters—

“junk DNA”

Figuring out the roles of this regulatory RNA is one of the most exciting projects of contemporary molecular biology.

neurogeny, that is to the embryonic development of the

we are far from understanding the behavioral effects of most drugs—from general anesthetics to stimulants to psychedelics—based on what is currently known about their membrane-receptor neurochemistry.

Whatever the details turn out to be, it is likely that the intricate structure of the cellular interior is involved in numerous aspects of the life process—up to and including mind and consciousness—that at this point we have little understanding of.

chemoaffinity hypothesis, proposing that nerve cells use specific chemical signals to guide their wiring during development and during neural regeneration.

Synapses that are not used are eliminated, a process called synaptic pruning.

neuroplasticity.

The hippocampus is a bilateral structure located beneath the surface of the temporal lobe known to play a pivotal role in the formation and stabilization of memories

Certainly a lesson from neuroscience is that experiences of infancy, childhood, adolescence, and early adulthood are likely the most powerful experiences of one’s life in terms of laying down pathways in the brain that will have lifelong effects on behavior.

A society that truly appreciates the importance of brain plasticity during the early years of life would place a very high priority on optimizing early learning.

Honeybees also have visual capacities that are unusual from a human perspective. Figure 11.5 shows an African daisy (Dimorphotheca aurantiaca) illuminated by sunlight and photographed with a lens that captures only visible light (left) and one that also captures ultraviolet light (right). Honeybee visual sensitivity extends into the ultraviolet region of the electromagnetic spectrum, a range of energies to which we humans are blind. There is abundant ultraviolet radiation in sunlight, and many flowers have patterns that are visible in ultraviolet light but are not noticeable as any sort of color difference in the visible region of the spectrum. These patterns are sometimes called nectar guides and are believed to act as visual features that attract bees and other pollinating insects and birds to them. Ultraviolet radiation is slightly higher in energy than visible light. The other direction on the electromagnetic spectrum, with radiation slightly lower in energy than visible light, is the infrared region. Infrared radiation also is not visible to us—its energy is too low to activate the photoreceptors in the eye. However, infrared radiation is absorbed by many molecules in such a way as to set them vibrating. This molecular vibratory motion, if it is strong enough, may be experienced as heat.

(Epithelium is the name given to the types of cells that line the surfaces of many structures throughout the body.)

1651. When we smell the aroma of the spice cinnamon, we are sniffing dozens of different molecules interacting with the 350 different types of olfactory receptor GPCRs in our nasal epithelium.

to learn a bunch of different names and structures but to appreciate that plant aromas are composed of dozens of different molecules that we inhale into our noses, which then activate various combinations of olfactory receptor proteins, and that from this our nervous

Here are two more molecules that have a stinky quality to them: methanethiol and dimethylsulfide. These molecules are found in the urine of many people who have eaten asparagus and impart a unique stinky aroma to the urine.

However, methanethiol and dimethylsulfide are not found in asparagus, either fresh or cooked. They are apparently produced during the digestive chemical transformation of molecules that are found in asparagus, such as asparagusic acid.

specific anosmia—

Hyperosmias are also possible,

Pheromones (Greek pherein = to carry, bear) are chemicals that carry signal information related to social communications between members of the

same species.

my money is on there being chemicals that are sensed by the human olfactory system and that trigger significant behavioral responses, including social attraction and repulsion.

Max Delbrück, in another context, coined the phrase “principle of limited sloppiness” to describe situations in experimental research where unexpected discoveries are made because a scientist is a little sloppy, but not so sloppy that he or she can’t figure out what has happened.

delicious (umai) and taste (mi).

Thus, the umami taste may have developed over the course of evolution to assist in the detection of protein-containing foods, important for survival.

The pungent or hot qualities of these plants are associated with molecular components that activate various receptors in the mouth. However, signals from these receptors enter the brain via pathways different from those associated with the primary tastes. They enter via the fifth cranial nerve (trigeminal nerve) and are received by regions of the brain closely associated with the perception of

Chili is experienced as “hot” because actual heat—that is, increases in temperature—is sensed by exactly the same molecular and cellular mechanism!

menthol. Menthol is appreciated for its distinctive flavor qualities, including producing a perception of a kind of “coolness.”

pepper, but not the same, is the pungency of mustard, horseradish, and wasabi. Associated with this particular perceptual quality of hotness is a family of molecules, the isothiocyanates,

Colors do not exist “out there” in the world—they are mental experiences related in some still mysterious way to how our nervous system responds to electromagnetic radiation having different energies.

This may be akin to the idea that aspects of contrast, shading, and texture may be better represented in black-and-white photography and cinematography than in the color versions.

and the origin of the metaphor of the blind spot: an area of one’s knowledge, belief, or behavior in which there is some significant ignorance to which one is oblivious.

scotoma

If the lesion is small, the scotoma may not even be noticeable to the patient, unless careful testing is conducted. If the lesion is sufficiently large, then the patient will experience an absence of information from part

of visual space. A large lesion might completely damage all of V1 in one hemisphere of the cortex, resulting in complete loss of vision for an entire half of the visual field, the half of visual space contralateral to the side of the brain in which the lesion is located. The clinical term to describe this is hemianopsia, meaning loss of vision in one half of visual space.

Sustaining a lesion in this area may bring on a clinical condition called prosopagnosia (Greek prosopon = face), in which the person has great difficulty or even a complete loss of ability to recognize faces. This is a very specific symptom; other aspects of visual perception remain intact.

Time will tell whether the vastly increased use of portable music players will lead to an increase in the prevalence of early-onset hearing loss.

A brain tumor is an anomalous, abnormal proliferation of cells in the brain. Such anomalous growth may be either benign (nonspreading) or malignant (able to metastasize and spread); the latter type of tumor has a much poorer prognosis.

One of the best-studied examples is Parkinson’s disease, a neurodegenerative condition characterized by slowness and difficulty with movement. Parkinson’s disease is associated with neuronal death in a specific region of the brain: the substantia nigra, one of the clusters of cells in the brainstem that uses dopamine as a neurotransmitter.

MRI uses not x-rays to penetrate the skull and other tissue but an entirely different process. It is based on a mysterious physical phenomenon called quantum spin.

Figure 17.2 MRI of a human brain.

or EEG. A graph of brain electric field changes as a function of time is called an electroencephalogram, sometimes referred to as a brain wave.

The magnetic fields associated with neural activity in the human brain measure about 1 picotesla (10–12 tesla) at the surface of the skull. This is a very small amplitude—Earth’s magnetic field, approximately 50 microteslas (50 × 10–6 tesla), is about fifty million times stronger. Ambient magnetic noise in an urban environment (due primarily to electricity moving through power lines and other wiring) is in the range of 0.1 microtesla

that no neuron in the human brain is more than a very small number of synapses away from every other neuron in the brain.

Prosopagnosia,

Cell layers in the human cerebral cortex made visible using Nissl stain (left), a dye that colors cell bodies but not axons and dendrites, and Golgi stain (right), which stains only a small fraction of the neurons but stains the axons and dendrites as well as the cell bodies. Drawings by Ramón y Cajal.

Such an aphasia of language production is often associated with lesions in the left frontal premotor area of the brain, a region called Broca’s area

Wernicke’s aphasia is a sensory agnosia specific to language.

twilight car hill frosted gasoline does remarkable planetary hum pizza.

Since its inception in 1949, the Wada test for the lateralization of language has been administered to thousands of patients as a prelude to brain surgery.

For non-right-handed (meaning left-handed and ambidextrous) people, approximately 70 percent have left-hemisphere language dominance, 15 percent have right-hemisphere language

Wernicke’s area may be considered a secondary or higher-order auditory area, involved in analysis of sounds with language-like properties.

Neurons in Broca’s area are in fact premotor mirror neurons, active when observing (reading, listening, and understanding) language, as well as when generating (writing and speaking) language.

anosognosia

The functions between the two hemispheres are not completely separated; it’s just that one hemisphere is more involved than the other for certain tasks.

as neural correlates of consciousness (NCC).

Thus, it is not straightforward to ask and obtain an answer to a question of the form: does the nonspeaking right hemisphere of a split-brain patient exhibit consciousness awareness? Or, more generally, is a patient in a coma or vegetative state consciously aware? What about when asleep, or while sedated by general anesthesia?

The human cerebral cortex—if it were to be unfolded, smoothing out all the gyri and sulci—is approximately 2.5 square feet, or 2,300 square centimeters, about the size of a circular pizza 21 inches in diameter.

neuropil

The notion that we will be able to figure out the human brain by mapping the locations of all the cells and all of their connections, and perhaps even construct a kind of replica using integrated circuits, vastly underestimates the nuance and complexity of what is going on.

Nonetheless, what is going on within the unfathomable complexity of neuropil, while intuitively graspable, is beyond detailed description within of our current understanding of neurophysiology.

brains are not “like” any artificial machine. If anything, they are “like” natural self-organizing processes such as stars and hurricanes. With the guidance and constraint of genes, they create and maintain their structures while exchanging matter and energy with their surrounds.

Freeman proposes that cerebrocortical neuropil may be described at the neurodynamic level as a uniquely unified system capable of undergoing something like “phase transitions” into states of global cooperativity,

These states of global cooperative synchrony are the neural correlates of consciousness.

Pathological memory problems are called amnesias, which come in two major categories: retrograde and anterograde.

One particular benzodiazepine, midazolam (Versed), is sometimes given in conjunction with medical procedures in which the patient is only partially anesthetized.

declarative and nondeclarative. Declarative memories can be brought to mind in words or describable images. This includes facts and other informational-type knowledge (semantic memory), as well as specific time-and-place events from one’s experience (episodic memory).

Advertising’s goal is that we learn and remember, without being aware that we are learning and remembering. In simple laboratory experiments, H.M. showed evidence of priming.

is, repeated activation of a network strengthens the synaptic connections within the network. Sometimes this is referred to as a Hebbian network.

reuptake

The networks of neurons that are activated depend upon what has been strengthened by

previous activation—

Hebbian networks. Thus, all past experience plays an essential role in determining the patterns

Meaning is a whole-body experience, and its foundation is memory.

the biological clock—

suprachiasmatic nucleus, or SCN.

14). The axon tract connecting these ganglion cells with the SCN is called the retinal-hypothalamic pathway,

Charles Darwin was a pioneer in the science of emotion. His book on The Expression of the Emotions in Man and Animals was published in 1872,

In the 1960s, the constructivist versus evolutionary perspective on emotion was tested by Paul Ekman (b. 1934), who compared the interpretation of facial expressions across different cultures.

Darwin’s discussion of human facial expressions drew upon the work of French neurologist Guillaume Duchenne (1806–1875), who studied the muscular control of facial expressions by selectively activating specific muscles using direct electrical stimulation.

The amygdala is also involved in signaling the hypothalamus to initiate a cascade of events that forms part of the body’s response to stressful events.

There has even been some exploration of these neuropeptides as drugs to increase prosocial behaviors in individuals suffering from conditions in which social connection is impaired—autistic spectrum disorders, depression, and schizophrenia, for example.

best-known reward circuit involves dopaminergic neurons in the ventral tegmental area projecting to the nucleus accumbens and the medial prefrontal cortex (Fig. 21.5).

euphorigenic

If one becomes stuck for a prolonged period of time (weeks, months, or more) in a mood state that significantly interferes with one’s ability to function and flourish in life, one is said to have a mood disorder.

reuptake

This came to be called the amine hypothesis of depression.

serotonin reuptake inhibitors (SSRIs).

Thorazine.

all had in common was antagonist action at dopamine receptors.

antidepressant medications, antipsychotic drugs currently generate billions of dollars per year in sales. Few would have predicted that psychiatric medications would become the economic juggernaut they are today?

While it may be the case that certain drugs facilitate changes in neural connections by perturbing brain physiology, real transformation comes from intention, action, and practice.

Darwin, in fact, was very much an advocate of goodness, compassion, and sympathy as important forces in human evolution—a kind of survival of the kindest. This he makes clear in his first book specifically about human evolution—The Descent of Man, and Selection in Relation to Sex—published in 1871,

In his marvelous 2009 book Born to Be Good,

Although it is true that human conflict is pervasive, humans also have highly refined emotional abilities to preempt and to resolve conflict. We excel at laughter, play, love, gratitude, compassion, and forgiveness. We are experts at cooperating with our fellow beings.

(telomere

Intelligence is from the Latin intelligentum, meaning to discern or comprehend, from inter + legere, to choose or pick out, from or between.

This is what is called reductionism—biology is explained in terms of (that is, reduced to) what is considered to be the more basic science of chemistry, and chemistry is understood in terms of the fundamental rules of matter and energy as described by physics, and physics is grounded in elegant mathematical structures and equations.

The transition from a superposition of potentialities to a discrete value is called a “reduction” or “collapse” of the wave function. It defines the connection between the microscopic quantum world of potentialities and the macroscopic classical world of our experience.

Does it mean that mathematical notions somehow exist as an intrinsic part of the foundation of reality? Are numbers—zero to infinity, real and imaginary, discrete and continuous—examples of what is really real, the “ideal forms” posited by the ancient Greek philosopher Plato (about 427–347 B.C.E.)? Or is mathematics, from

the simple to the profoundly esoteric, solely a product of human cognition—our concept of numbers, ability to carry out mathematical operations, and capacity to formulate and discover mathematical truths (such as “π is an irrational number,” “there is no largest prime number,” or “xn + yn = zn has no integer solutions x, y, z for any integer value of n > 2”)—directly related to biological evolution of our cognitive capacities and nothing more?

This could give rise over time to the formation of stabilized, energy-using, replicating systems—life as we know

it.

(How subjectivity is related to the physical workings of the brain and body is sometimes called the hard problem of

consciousness research. It is also referred to as the explanatory gap between the physical and the subjective.)

2. Refined analysis of mental experience, drawing from the tools of contemplative traditions, and in particular the current dialogue between science and Buddhism

neuromorphic computers.

We fantasize about communicating with aliens from another star system. Perhaps we ought also work on communicating with the likely very sentient and very intelligent aliens among us.

one scenario (due to Roger Penrose and Stuart Hameroff) posits that subcellular structures such as microtubules may be information storage and computational devices, with aspects of their component tubulin structures acting something like information bits in a computer.

The faculty of bringing back a wandering attention, over and over again, is the very root of judgment, character, and will. . . . An education which should improve this faculty

would be the education par excellence. But it is easier to define this ideal than to give practical directions for bringing it about.

physical science, interconnecting the two domains in new and unexpected ways. This would be a truly revolutionary development in science, on par with the greatest scientific revolutions

Nagel (1974).

Nagel, T. (1974). What is like to be a bat? Philosophical Review, 83, 435–450.

Parkinson’s disease, 198, 260

The Birth of Intersubjectivity: Psychodynamics, Neurobiology, and the Self MASSIMO AMMANITI, VITTORIO GALLESE

In a broad sense, all disease is experienced through the nervous system.

It’s all in your head, whether it’s mental confusion or a skinned knee.

communicate, whereas

There are many types of neurotransmitters; most of the ones you know already are small peptides such as acetylcholine, GABA, glutamate, serotonin, and the catecholamines (dopamine, epinephrine, and norepinephrine).

“apraxic.”

Nasolabial fold flattening

They decussate (or cross) in the medulla at the medullary pyramids, right where the brainstem meets the spinal cord;

extrapyramidal system, runs outside the medullary pyramids (hence extrapyramidal) and includes neurons within the basal ganglia and cerebellum, among other locations. Unlike the neurons of the pyramidal system, these neurons synapse all over the place and are important for indirect, largely involuntary, modulation, coordination, and regulation of movements.

Dopamine depletion within the basal ganglia, for instance, as in Parkinson disease, can result in tremor and bradykinesia (slowness of movement).

Extrapyramidal dysfunction is responsible for many of the manifestations of Parkinson disease, including tremor, abnormal posture, and gait dysfunction.

“confrontation testing.”

eyes closed, patients can only rely on proprioception, so if proprioception is impaired, they will lose their balance.

dysmetria.

Ataxic gait.

Shuffling gait.

Classic for Parkinson disease, this type of gait can also be seen in normal pressure hydrocephalus. It is characterized by small short steps with very little foot elevation off the ground.

where, anatomically, they come from (or, in neurologist speak, “localize to”).

LP, EEG, and EMG/ NCS—form the crux of the diagnostic toolbox for neurologic disease.

Radiologists use the term “intensity” as opposed to “density” to describe brightness on an MRI: things that appear bright are referred to as “hyperintense” (or “increased signal”), and things that appear dark are “hypointense” (or “decreased signal”).

this is why posterior communicating artery aneurysms can cause third nerve palsies!

cytokines.

Trigeminal Autonomic Cephalalgias (TACs)

Trigeminal nerve distributions: V1 (ophthalmic), V2 (maxillary), V3 (mandibular).

SUNCT (short-lasting unilateral neuralgiform headache with conjunctival injection and tearing) and SUNA (short-lasting unilateral neuralgiform headache with autonomic symptoms).

These headaches are characterized by sudden attacks of stabbing, unilateral pain that last only a few seconds but can occur hundreds of times a day. The attacks are often triggered by tactile or cutaneous stimuli, such as bathing, brushing one’s hair, or shaving. SUNCT presents with both conjunctival injection and tearing;

Lamotrigine

Preventive Treatment Lamotrigine Indomethacin Verapamil, Galcanezumab Indomethacin

diagnosis, in reality very few headaches are directly associated with acute or chronic sinusitis.

Pain around the sinuses, without evidence of an upper respiratory infection, is rarely a sinus headache, but far more often a manifestation of migraine.

Trigeminal Neuralgia

(TN), TN presents with unilateral, brief episodes of shock-like pain that occur in the distribution of one or more divisions of the trigeminal nerve; the maxillary and mandibular branches (V2 and V3) are more commonly affected than the ophthalmic division (V1).

Classical TN. Classical TN is due to neurovascular compression causing morphological changes in the trigeminal nerve root. An abnormal vascular loop compresses the trigeminal nerve around its dorsal

Secondary TN.

This refers to TN caused by an underlying disease,

Carbamazepine and oxcarbazepine are commonly used treatments for classical and idiopathic TN.

gabapentin

Fifteen percent of patients with MCI over the age of 65 will go on to develop overt dementia within 2 years; this statistic can unnerve even the most stoical among your patients, so remember to emphasize to them that this means that 85% of people with MCI will not progress to dementia during that period.

allele.

The pathology involves the loss of primarily dopaminergic neurons within the substantia nigra (a part of the basal ganglia located in the midbrain), as well as the destruction of neurons, both dopaminergic and otherwise, in other areas of the brain.

PD causes four classic physical signs that are the result of involvement of the extrapyramidal motor system, the part of the motor system involved in modulation and regulation of movement:

akinesia for the often more accurate bradykinesia).

The extrapyramidal system is everything else that impacts movement, and includes neurons within the basal ganglia and cerebellum. In general, the pyramidal system causes voluntary movement, whereas the extrapyramidal system causes involuntary movement, indirectly regulating and modulating the activity of the pyramidal system. See page 18 for a more comprehensive review of motor system anatomy.

unilaterally and then spreads contralaterally over a course of months to years.

To be clear, though, don’t be confused by the seemingly contradictory prefixes: although the rigidity associated with PD is a form of hypertonia, PD itself is a hypokinetic movement disorder, that is, characterized by the loss of movement.

Bradyphrenia,

Neuropsychiatric difficulties range from issues with impulse control (often worsened by dopamine agonist therapy used to treat PD; see page 339), anxiety, and depression to frank psychosis with hallucinations, memory loss, and dementia.

A favorable response to a levodopa challenge will clinch the diagnosis of PD and can often effectively rule out the atypical parkinsonisms (see page 342).

To reiterate, PD is a clinical diagnosis. MRI is not necessary in patients with classic symptoms and a good response to levodopa, but it may be useful to exclude secondary causes (see page 344) in patients with atypical presentations of the disease. More advanced MRI techniques, such as MR spectroscopy and diffusion tensor imaging, may offer higher sensitivity for detecting PD-related neurodegeneration, but their efficacy and diagnostic utility remain unknown. DaTscan, a specific type of single-photon emission computed tomography (SPECT) scan, enables visualization of dopamine transporter levels in the brain and can help distinguish patients with PD or atypical PD syndromes from patients with other diseases such as essential tremor. These scans cannot, however, distinguish between PD and atypical PD syndromes.

carbidopa, a dopa decarboxylase inhibitor that prevents the peripheral conversion of levodopa into dopamine. The combination of these two agents has been the basis of therapy for PD for

Other agents can be added as adjunctive treatment for patients who are no longer adequately responding to levodopa-carbidopa alone:

Dopamine agonists (pramipexole, ropinirole, or bromocriptine). These can cause sedation, lower extremity edema, and impulse control issues. MAO-B inhibitors (selegiline, safinamide, or rasagiline). Insomnia is a common side effect. COMT inhibitors (entacapone or tolcapone). COMT (Catechol-O-methyl transferase) is an enzyme that breaks down both dopamine and levodopa. COMT inhibitors therefore prolong the half-life of levodopa. They can cause gastrointestinal side effects, sleepiness, and urine discoloration (to dark yellow or orange; this is benign but can be upsetting if patients are not warned beforehand!). Liver function tests must be monitored in patients on tolcapone.

There is good evidence that starting exercise early, including balance and gait training, resistance and strength exercises, and aerobic exercise, can help patients maintain and often improve their motor function.

No pharmacologic treatment has yet been shown to alter the natural history of the disease.

Despite maximal therapy, most patients will ultimately develop disabling complications. Dementia is common, affecting a significant minority of patients within 5 years. By 10 years, about 25% of patients will require nursing assistance, and average life expectancy from the time of diagnosis is less than 10 years.

Propranolol (a beta blocker) and primidone (an anticonvulsant) are the first-line drugs when medication is required, but they are typically only effective for mild cases.

13.8 For those of you with a good sense of timing, you may be able to discern that the tremor of ET is faster than the tremor of PD, typically 8 to 10 Hz (i.e., 8 to 10 cycles per second) compared with only 3 to 7 Hz.

common; patients with early PD are often initially thought to have essential tremor.

major types of atypical parkinsonian syndromes are:

Progressive supranuclear palsy Corticobasal degeneration Dementia with Lewy bodies Multiple system atrophy

Magnetic resonance imaging (MRI) classically shows prominent midbrain atrophy resulting in what’s known as the “hummingbird sign.”

St. Vitus dance

monoamine neurotransmitters include dopamine, epinephrine, norepinephrine, and serotonin;

Hiccups (diaphragmatic myoclonus) and hypnic myoclonus (the sudden jerk many people get just as they are starting to fall asleep) are examples of physiologic myoclonus.

hypnic myoclonus, the myoclonic jerks that accompany falling asleep or transitions from one stage of sleep to another.

Follow-up on Your Patient: You immediately suspect that Suzanne has Parkinson disease because of her shuffling gait and unilateral resting tremor. Your examination also reveals cogwheel rigidity in her right upper extremity and a positive pull test. Her cognitive testing is normal. You tell her she has Parkinson disease and discuss starting treatment with levodopa-carbidopa. Because her symptoms are interfering with her work in the hospital, she agrees and begins treatment immediately. One month later in follow-up she reports that the medication has helped her immensely and she has been able to continue working much as she has become accustomed to. You arrange to see her on a regular basis to monitor her symptoms and medication.

How to diagnose and treat patients with Parkinson disease. The mnemonic TRAP (commit this to memory!) that summarizes the basic manifestations of Parkinson disease.

Vasogenic edema is caused by the breakdown of the blood-brain barrier.

Cytotoxic edema is the result of cell death.

CSF

Altered mental status (AMS)

Like AMS, encephalopathy is a vague term that is often defined as any sort of “brain malfunctioning.”

postictal

Vladimir Nabokov1, author of Lolita, Ada, and Pale Fire, and physicist Richard Feynman are both believed to have been synesthetes.

hyponatremia,

is no

pica behaviors (eating items not normally considered food, such as dirt or grass)

chelation

AMS.

Altered mental state.

Brain tumors are mass lesions: they take up space inside the skull.

Because the brain atrophies over time, older patients tend to have more space inside their skull and can therefore “hide” mass lesions for longer

than younger patients, who have very little extra space and tend to become symptomatic earlier.

Primary brain tumors (i.e., tumors that originate in the brain) are actually significantly less common than metastatic brain tumors (i.e., tumors that originate elsewhere in the body).

nicardipine

The pathway below explains why it’s a consensual reflex: that is, why, if you shine light in one eye, both eyes will constrict.

Parkinson disease (PD)