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The Footprints of
The bits and pieces of the brain that render us
conscious reside in places few suspected

By Christof Koch

“It is in the brain that the poppy is red, that the apple is odorous, that the skylark sings.”
— Oscar Wilde (1854–1900)

e moderns take it for granted that consciousness is intimately tied up with

the brain. But this assumption did not always hold. For much of recorded h ­ istory,
the heart was considered the seat of reason, emotion, valor and mind. Indeed, the
first step in mummification in ancient Egypt was to scoop out the brain through
the nostrils and discard it, whereas the heart, the liver and other internal organs
were carefully extracted and preserved. The pharaoh would then have access to ev-
erything he needed in his afterlife. Everything except for his brain!
Several millennia later Aristotle, one of the greatest of all biologists, taxonomists,
embryologists and the first evolutionist, had this to say: “And of course, the brain is
not responsible for any of the sensations at all. The correct view [is] that the seat and
source of sensation is the region of the heart.” He argued consistently that the ­primary
function of the wet and cold brain is to cool the warm blood coming from the heart.
Another set of historical texts is no more insightful on this question. The Old and the
New Testaments are filled with references to the heart but entirely devoid of any men-
tions of the brain.
Early debate about what the brain does has grown ever more intense over ensu-
ing millennia. The modern embodiment of these arguments seeks to identify precise
areas within the three-pound cranial mass from where consciousness arises. What
follows is an attempt to size up the past and present of this transmillennial journey.
The field has scored successes in delineating a brain region that keeps the neural
engine humming. Switched on, you are awake and conscious. In another setting, your


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body is asleep, yet you still have experi- scientist by testing the hypothesis that ble for carrying out specific functions.
ences — you dream. In a third position, the brain controls all muscles by means Locationism rose to dominance after
you are deeply asleep, effectively off- of the nerves. Famously, Galen argued 1861, when French neurologist Paul Br-
line. What is more, I and others have la- that the vital spirit that animates hu- oca presented the landmark case of a pa-
bored on discovering critical brain re- mans flows up from the liver to the heart tient unable to speak except for a single
gions that imbue us with specific forms and into the head. There, inside the ven- word. The patient’s brain exhibited
of conscious experience: perceptions of tricles— the brain’s interconnected fluid- widespread damage to the left inferior
the orange hues of a sunset, pangs of filled cavities — the vital spirit becomes frontal gyrus, part of the neocortex that
hunger or the stabbing pain of a tooth- purified and gives rise to thought, sensa- crowns the top part of the brain. An
ache. Those are in the neocortex, the tion and movement. analysis of a second patient reinforced

D E A /C. S A PPA G e t t y I m a g e s (1); D E A /A . D A G L I O R T I G e t t y I m a g e s (2); W O R L D H I S T O R Y A R C H I V E A l a my (3); I N T E R F O T O A l a my (4 )

brain’s outer surface that generates the For more than 12 centuries after- Broca’s conclusion that this small region
particular c ontent o
 f experience as it ward, the world plunged back into dog- was responsible for productive speech
plays out from one moment to the next. ma, mumbo jumbo, exorcism and mys- (touch the bottom of your left temple to
ticism until the beginning of the Europe- get an idea of where it is). The identifica-
From Heart to Head an Enlightenment. The publication of tion of this region, which has been
By and large, classical Greece and C erebri anatome in 1664 by the English named Broca’s area, also fortified the
Rome were in thrall to cardio-centric doctor Thomas Willis heralded the be- view of the neocortex as the jewel in the
thinking. The brain proper looked too ginning of today’s neuro-centric age, crown of the central nervous system, the
mushy, coarse and cold to host the sub- with its meticulous drawings (by the region most closely associated with
lime soul. Yet some clinicians and anat- young Christopher Wren, England’s higher-order cognitive functions, in-
omists had already deduced that the most acclaimed architect) of the brain’s cluding consciousness.
brain was intimately tied to sensation convolutions that transcended previous In those early days during the Sec-
and movement. Two remarkable exam- renditions, which greatly resembled a ond Empire in France, doctors depend-
ples are the fourth-century B.C. work by tangle of intestines. ed on astute observations of symptoms
Hippocrates — On the Sacred Disease— Neuroscience has always retained a and on dissection of the brains of pa-
that combines a rejection of superstition creative tension between holists, who ar- tients who had died to reliably infer the
in treating brain disorders with an accu- gue that mental activity and other brain site of a lesion and connect it to its like-
rate clinical description of epilepsy. Lat- functions cannot be tied to a specific re- ly function. Today neurologists can
er, in second-century A.D. Rome, the re- gion in the brain, and locationists, who make these connections by directly peer-
nowned Greek physician Galen became, claim that specific loci, hot spots in the ing inside the heads of their living pa-
in essence, the first experimental neuro- language of brain imagers, are responsi- tients using x-ray computed tomogra-
phy, magnetic resonance imaging and
other powerful imaging techniques.
Damage to the brain comes in many
forms: strokes, hemorrhages, tumors,
Until the 17th century, widespread beliefs held that the heart was the seat of sensation,
viruses, bullets and blows. Examining
volition and the soul.
such destruction, when limited in scope,
It took until the 1980s for studies on the nature and physiology of consciousness to become
more than a theoretical exercise. can illuminate the link between the
Research has demonstrated that regions in the lower brain—the brain stem—are necessary brain’s complex structure and what hap-
for switching on activity in areas devoted to higher cognitive functions. pens when a particular region shuts
A posterior area of the brain appears to be key for conscious seeing, hearing and feeling. down. Interpreted carefully, such clini-

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The quest for the seat of consciousness began
in all the wrong places. Embalming procedures
in ancient Egypt (1) discarded the brain be­cause
it was thought that the heart, liver and other
organs hosted the soul. Hippocrates and Galen,
physicians from antiquity depicted in a 13th-cen-
tury fresco (2), realized that the brain controlled
our thoughts and actions. During the Renais-
sance, Andreas Vesalius, credited as the father of
modern anatomy, captured details of the brain’s
surface (3), a prelude to René Descartes’s specu-
lation that the pineal gland (onion-shaped struc-
ture, 4) is where consciousness resides.

cal studies have by far been the most fe- pressed, consciousness will flee the vic- During and after World War I, a re-
cund source of knowledge concerning tim. Indeed, even a small injury to parts markable wave of “sleepy sickness,” or
the relation between the physical brain of it can lead to a profound and sus- encephalitis lethargica, swept the world.
and the conscious mind. tained loss of consciousness. The patient The condition helped to point to the
can go into stupor and can only be par- brain stem as a mediator of sleep and
© I S T O C K .C O M (b o t t o m)

The Brain’s Light Switch tially aroused after vigorous and pro- wakefulness. This form of encephalitis
Some areas of the brain are more in- longed stimulation. Worse, the patient induced in many of its victims a state of
strumental than others in generating a can lapse into a coma, an enduring, almost permanent and statuelike sleep,
conscious state. The brain stem at the sleeplike state of immobility with closed from which they would awaken only for
top of the spinal cord is one of them. If eyes, from which arousal may prove to a few hours at a time. It was the astute
the brain stem is damaged or com- be difficult. observation by the Austrian neurologist

Occipital Cortex
A Guided Tour Broca’s Area
Visual information about form and
Scientists fall into two In 1861 Paul Broca discovered a small region
motion gets processed in this area at
camps when discussing at the brain’s surface that is responsible for
the back of the brain.
the brain. Holists argue producing speech.
that consciousness is gen-
erated by the entire three-
pound mass made up of
170 billion cells, of which
half are nerve cells. Loca-
tionists support the idea
that specific neural circuits Left Fusiform Gyrus
are responsible for specific When stimulated, this
functions, including con- area produces flashes
sciousness. On closer of light but not the
inspection, neuroanato- facial imagery that
mists have realized that emerges when the
one confined area, the right fusiform gyrus,
brain stem, ensures that on the opposite side,
we do not lapse into a coma is activated.
or suffer from a sleeping
sickness. Meanwhile rear
areas on the surface of the
brain are needed to gener-
ate mental imagery and oth-
er specific conscious expe- Cerebellum
riences, such as Brain Stem This mini brainlike structure
recognizing your enables precise motor
Neurons in the brain stem con-
grandmother. control. Lesions in part
trol the level of arousal or wake-
of the cerebellum do not
fulness. If these do not properly
appear to lead to a loss of
function, the patient lapses into
conscious experiences.
stupor or a coma or may die.


Baron Constantin von Economo of vic- control internal bodily processes, such as and its connection to consciousness.
tims of this epidemic, which led to the breathing, thermal regulation, muscle When we began this labor of love in
hypothesis that a brain center in the hy- tone, heart rate, and so on and process the late 1980s, writing about conscious-
pothalamus actively promotes sleep, signals relating to the working condition ness was viewed as a fringy subject, a
whereas another in the upper brain stem of the body’s organs. sign of a scientist’s cognitive decline. Re-
produces wakefulness. Brain stem neurons promote con- tired Nobel laureates did it, as did phi-
A more precise localization came sciousness by suffusing the cortex with losophers and mystics, but not hard-core
from classical experiments by Italian Gi- the proper cocktail of these neurochem- scientists. When the topic arose, gradu-
useppe Moruzzi and American Horace icals to keep cortical neurons in an ate students, always finely attuned to the
Magoun in the late 1940s, demonstrat- aroused state. These substances alone mores and attitudes of their elders,
ing that a brain stem region known as are incapable of producing an experi- rolled their eyes and smiled indulgently.
ence. Rather they form the back- Betraying an interest in consciousness
ground — a neural palette — on was ill advised for a young professor,
which any conscious experience particularly one who had not yet at-
occurs, and this chemical mix acts tained the holy state of tenure.
When we began as a “switch.” But if the cortex is Those attitudes have since changed.
this labor of love in the severely damaged, it cannot receive Together with a handful of colleagues,
late 1980s, conscious­ the signals that keep the light of
conscious experience in the requi-
Crick and I gave birth to a science of con-
sciousness. Its physical basis in the brain
ness was viewed as site “on” state. Patients with brain is now investigated worldwide, and ques-
a fringy subject, a sign stem function that has been rela- tions concerning what makes any system,
tively spared but widespread corti- biological or man-made, exhibit a con-
of a scientist’s cal destruction typically remain in scious state are hotly debated. Conscious-
cognitive decline. a vegetative state, permanently un- ness is no longer the unspoken taboo.
responsive but with eyes open, ex- Our goal from the outset was to iden-
periencing or feeling nothing. tify the mechanisms in the brain that, at
a minimum, are needed to create a spe-
the midbrain reticular formation modu- Where Consciousness Resides cific conscious experience: seeing the set-
lates the level of wakefulness (“reticu- At this point, the story gets personal. ting sun, recognizing your grandmother
lar” here refers to the mesh or netlike ap- In the late 1980s, as a freshly baked as- or feeling that god-awful toothache. We
pearance of this part of the brain). sistant professor at the California Insti- called these the “neuronal correlates of
In more recent years this notion of a tute of Technology, I started having reg- consciousness,” or NCC. What exactly
monolithic system that activates con- ular conversations with Francis Crick is an NCC was by no means clear. Must,
sciousness has given way to a recognition about the mind-body problem. Crick for instance, some nerve cells vibrate at
that 40 or more nuclei are housed with- was the physical chemist who, together a particular magical frequency? And if
in the brain stem, all of which exhibit a with James Watson, discovered in 1953 that is true, what is it about the biophys-
specific neurochemical identity. These the double-helical structure of DNA, the ics of particular bits and pieces of high-
conglomerations of neurons are pro- molecule of heredity. In 1976, at age 60, ly excitable brain matter vibrating at a
foundly different in structure from the when Crick’s interests shifted from mo- specific frequency that is able to produce
layered organization of the cortex. Cells lecular biology to neuroscience, he left the glorious surround sound and Tech-
in different nuclei manufacture, store Cambridge, England, in the Old World nicolor that constitute the sounds and
and release different neurotransmitters to establish his new home in La Jolla, Ca- sights of life? Are these special con-
or neuromodulators at their synaptic ter- lif. Despite an age difference of 40 years, sciousness neurons all located in a par-
minals — acetylcholine, serotonin, nor- Crick and I struck up an easy friendship ticular part of the brain, as René Des-
adrenaline, GABA, histamine and orex- and a collaboration that would last for cartes famously postulated back in the
in. Many of these brain stem nuclei mon- 16 years and result in two dozen scien­ middle of the 17th century for the pine-
itor and modulate our conscious state, tific papers, essays and two books. al gland, probably the first hypothesized
including wake-to-sleep transitions. All of them focused on the anatomy neuronal correlate of consciousness?
Collectively they transmit signals that and physiology of the mammalian brain It is important to stress the “mini-
mal” in defining the NCC. Without that
qualifier, all of the brain could be consid-
ered a correlate: after all, the brain does
CHRISTOF KOCH is president and chief scientific officer at the Allen Institute for Brain generate consciousness, day in and day
Science in Seattle. He serves on S
 cientific American Mind’s board of advisers. out. But Crick and I wanted to find the

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specific synapses, neurons and circuits and colors but not keys. Yet if she grasps ognition in volunteers within regions of
that generate — that, in fact, c ause— an them or if they are jingled, she immedi- the ventral temporal cortex, called the fu-
equally specific conscious experience. Be- ately knows what they are. Poetically siform gyri (bottom area toward the back
ing careful scientists, we used the more termed Seelenblindheit in German (lit- of the head). Found bilaterally, the re-
cautious “correlates” in place of the more erally, “blindness of the soul”), this con- gions are referred to as the fusiform face
definitive “causes” of consciousness. dition was rechristened agnosia by Sig- area and respond more strongly to pic-
Based on our knowledge of the high- mund Freud, a term that persists. The tures of faces, compared with scrambled
ly sophisticated nature of cortical nerve late neurologist Oliver Sacks brilliantly faces or other objects and scenes.
cells and their response to stimuli in the wrote about patients with agnosia and Epileptic patients have played an out-
external world, we set our sights on the how their loss shaped the way they expe- sized role in consciousness research. This
cortex, the gray matter on the brain’s rienced the world. is especially true of those who ha elec-
outer surface. The cortex is a laminated Consider A.R., who suffered a block- trodes implanted to control their sei-
sheet of nervous tissue about the size of age to the cerebral artery that damaged zures. A study of 10 such patients con-
a large pizza. Two of these sheets are a small region on one side of his occipi- ducted in 2014 at Stanford University
crammed into the skull, side by side, tal cortex. The stroke briefly blinded used the electrical signals recorded by
making up the left and right cortical him. He eventually recovered sight but implanted electrodes to confirm that
hemispheres. The cortex is subdivided permanently lost color vision in the up- both the left and the right fusiform gyri
into the neocortex – a defining hallmark per left quadrant of his field of view, cor- responded selectively to faces, compared

The brain stem (left, highlighted in yellow), serves as an engine of consciousness. When injured, it may extinguish all conscious activity. The
modern search for key brain loci that imbue us with consciousness began with Francis Crick, the author’s mentor, decades after he had co-
discovered the structure of DNA.
G E T T Y I M A G E S (l e f t ); D A N I E L M O R DZ I N S K I G e t t y I m a g e s (r i g h t )

of mammals – and the evolutionary old- responding to the site of a pea-sized le- with pictures of body parts, cars or hous-
er archicortex. All available evidence sion in his right occipital visual cortex. es. These electrodes could also directly
points toward certain key regions with- A.R.’s low-level vision — detection of excite the underlying cortical tissue us-
in the 300 grams of highly structured brightness, lines, and so on— and his mo- ing electrical pulses. Stimulating the
neocortical tissue as the location of con- tion and depth perception were normal. right fusiform gyrus led to reports of per-
tent-specific NCCs. The only other deficit was a difficulty to ceiving faces. In one study a patient who
Lesions to the rear section of the distinguish forms — he could not read looked at his neurologist remarked:
neocortex— for instance, from a stroke text — but this problem was confined “You just turned into someone else. Your
or some other damage — demonstrate again, to the upper left quadrant. face metamorphosed. Your nose got sag-
what happens when activity in the back Functional MRI and EEG are some of gy and went to the left. You almost
of the brain shuts down. A patient so af- the most common ways to look for neu- looked like somebody I’d seen before but
flicted cannot recognize a set of keys on ral correlates of consciousness in healthy somebody different. That was a trip.”
a chain dangling in front of her. She volunteers. These techniques can identify [see illustration on page 59].
looks at them and sees texture and lines a bevy of brain areas related to face rec- When the left fusiform gyrus was

M I N D. S C I E N T I F I C A M E R I C A N .C O M  S C I E N T I F I C A M E R I C A N M I N D  57
stimulated, patients either did not make Consider the rare, and extreme,
such reports, or they were restricted to case of a 24-year-old woman born Large portions of
simple, nonface imagery, such as twin- without a cerebellum altogether
kling and flashing of light or traveling [see right illustration below]. the front of the brain
blue and white balls. She has mild mental impair- can be excised without
This study underscores the truth be- ment and moderate motor deficits
hind the oft-repeated mantra that corre- and talks with a mild tremor. Yet
having a major impact
lation is not causation. Just because the she clearly speaks about her daily on conscious
left fusiform gyrus is selectively activat- experiences, her likes and dislikes, experience.
ed by a sight, sound or action, that does and her life with a young daughter.
not imply that the area is essential for vi- Yet unlike the rest of us, she has no
sion, hearing or movement. These pa- cerebellum at all; only a cavern
tients also teach us that electrically stim- filled with cerebral spinal fluid
ulating the right ventral temporal cortex shows up in her brain scan. Indeed, it is common surgical
can give rise to imagined faces. Indeed, This absence is remarkable because knowledge that removing much of the
this region is the best candidate we have the cerebellum contains Purkinje cells, front of the cortex causes no apparent
for a content-specific NCC like “seeing” whose fan-shaped structures are among major deficit! This surprising realiza-
a face. Its activity correlates closely and the most beautiful and complex of all tion stems from insight gained from
systematically with facial perception. neurons. And astonishingly another cell hundreds of neurosurgeries for tumors,
Stimulation of it induces or alters the type in the cerebellum— the granule neu- epileptic seizures and other neurologi-
perception of faces, and, crucially, peo- ron— outnumbers cortical ones by a fac- cal conditions during the first half of

C L I N I C A L A N D I M A G I N G F I N D I N G S I N A L I V I N G PAT I E N T,” B Y F E N G Y U E T A L ., I N B R A I N. P U B L I S H E D O N L I N E A U G U S T 2 2, 2 0 14 (r i g h t )
A J PHO T O G e t t y I m a g e s (l e f t ); F R O M “A N E W C A S E O F C O M P L E T E P R I M A R Y C E R E B E L L A R A G E N E S I S:
ple become face-blind when this region tor of four. Despite this intricate physi- Tools in the hunt for consciousness include
is destroyed. ology, neural activity in the cerebellum EEG (left) and MRI brain scans (right).
These scans show a woman with an empty
For consciousness researchers, some- does not give rise to consciousness. space where her cerebellum should be.
times where you do not find something Even more intriguing than the cere-
becomes a critical goal. This observation bellum are the frontal lobes of the neo-
applies to the cerebellum, tucked below cortex. Traditionally they are thought to the 20th century, when neurosurgeons
the cortex at the back of the brain, and be the key hallmark of our species, hav- routinely excised large swathes of fron-
even pertains to parts of the cortex. ing expanded more in Homo sapiens tal or prefrontal cortex on both sides.
If the cerebellum is damaged, both than in all other higher primates. Func- What is remarkable is how unremark-
animals and people have difficulty mak- tional brain imaging has also shown able these patients appear from their
ing precise movements, and the move- them to be involved in tasks that involve clinical description.
ments they do make lose precision and planning, short-term memory, lan- The most dramatic example is Mr. A,
become erratic, jerky and uncoordinat- guage, reasoning and self-monitoring. a patient of neurosurgeon Walter Dandy
ed. Yet patients with cerebellar lesions Yet more than a century of reports de- in 1930. Because of Mr. A.’s massive tu-
do not complain of being unable to see, scribing electrical brain stimulation car- mor, the surgeon had to amputate the pa-
hear or feel. Nor do they experience ried out during neurosurgery while the tient’s frontal poles, the protruding sec-
transient or permanent loss of con- patient is awake suggest that it is diffi- tions at the front of the brain. The patient
sciousness. Their subjective experience cult to directly elicit sensory experienc- survived this bilateral frontal lobectomy
of the world appears intact and normal. es from stimulation of frontal sites. for 19 years and continued to speak. A

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Now You See Me, Now You Don’t
Electrical stimulation of the right fusiform gyrus, seen from below, in four epileptic patients undergoing surgery caused distorted perception
of faces. The red dots represent electrodes that produced distorted views, whereas the blue ones, set farther away, did not in one patient.

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“Like you weren’t you. You “You turned into someone “That orange part looked like “[The eye] looked like
were a different person. I else. Your face metamor- a person ... like a face and a a circle and then changed
noticed the eyes. I was able phosed.... Your nose got body.... Like a hallucination to a rectangle shape.”
to see almost your whole saggy and went to the left.” of the curtains.”
body on your right side.”
E F F EC T S I N C O N S C I O U S FA C E P E R C E P T I O N ,” B Y V I N I T H A R A N G A R A J A N E T A L ., I N J O U R N A L O F N EU R O S C I E N C E ,

note in his file observed that “one of the might then be involved in unconscious brain that make us conscious appear to be
S O U R C E : “ E L EC T R I C A L S T I M U L AT I O N O F T H E L E F T A N D R I G H T H U M A N F U S I F O R M GY R U S C A U S E S D I F F E R E N T

salient traits of Mr. A’s case was his abil- planning, strategizing, forming memo- centered on a more restricted hot zone in
ity to pass as an ordinary person under ries and focusing attention. the posterior part of the neocortex, with
casual circumstance.” When he toured some possible additional contributions
the Neurological Institute in the compa- The Hot Zone from some anterior regions.
VO L . 3 4, N O. 3 8; S E P T E M B E R 17, 2 0 14; D E A G O S T I N I P I C T U R E L I B R A R Y G e t t y I m a g e s (b r a i n)

ny of distinguished neurologists, “no one Since the modern quest for the NCCs These findings raise the question of
noticed anything unusual.” Mr. A. did at the end of the 20th century, progress why the seats of consciousness are so cir-
exhibit some of the behaviors associated has been rapid compared with previous cumscribed. Is there something so differ-
with frontal lobe removal, such as child- millennia. First, conceptual work has ent in the wiring or behavior of neurons
like behavior, lack of inhibition and a clarified the importance of investigating in the back of the cortex from those in the
need to tell jokes. Neither he nor other pa- the neural correlates of both specific con- front? Future investigations will be need-
tients who submitted to similar surgeries scious contents and consciousness as a ed in the decades — maybe centuries —
were robbed of conscious behaviors. whole. Second, some parts of the brain ahead to further illuminate the types of
Their capacity to see, hear or experience have been identified as contributing little neural activity that underlie the infinite
the world remained intact, despite the to conscious experience. The areas of the varieties of human experience.  M
drastic surgical intervention.
That the anterior cortex may not be
necessary for sensory consciousness does MORE TO EXPLORE
not imply that it does not contribute di- ■ ■ Brain
of Patient A. after Bilateral Frontal Lobectomy; Status of Frontal-Lobe Problem.
rectly to any given aspect of conscious- R. M. Brickner in A
 MA Archives of Neurology and Psychiatry, V
 ol. 68, No. 3, pages 293–313; 1952.
ness. After all, being self-conscious (re- ■ ■ Electrical
Stimulation of the Human Brain: Perceptual and Behavioral Phenomena
Reported in the Old and New Literature. A. Selimbeyoglu and J. Parvizi in F
 rontiers in Human
flecting on what one perceives) is differ-
Neuroscience, Vol. 4, Article 46, pages 1–11; May 2010.
ent from perceiving something, yet both ■ ■ The
Neural Correlates of Consciousness: Progress and Problems. C. Koch, M. Massimini,
are subjective experiences. Perhaps re- M. Boly and G. Tononi in N
 ature Reviews Neuroscience, V
 ol. 17, pages 307–321; May 2016.
flection, effort, and so on are generated From Our Archives
by the anterior cortex, although no firm ■ ■ The Face as Entryway to the Self. Christof Koch; Consciousness Redux, January/February 2015.
evidence exists yet. The prefrontal cortex ■ ■ Sleeping While Awake. Christof Koch; Consciousness Redux, November/December 2016.