ABSTRACT
Neurobiological investigations are rapidly approaching, or perhaps have even
reached, the size scale at which quantum phenomena may be observable. One such
phenomenon is the collapse of the quantum wave function, which one school of
physics has long thought to be a brain process. In this commentary, possible
neural mechanisms of wave function collapse and their relation to human
conscious experience are considered, as well as their potential involvement in
neuropathologies that may be quantum mechanical in nature. Other
interpretations of quantum mechanics and their relevance to neuroscience are
also discussed.
INTRODUCTION
Neuroscience has largely committed itself to the paradigms
of molecular biology. The Human Genome Project will eventually provide a
catalog of the genes that ultimately regulate the production of every human
character, including cognitive behavior. With that map and with the new
interventionist strategies of gene therapy and genetic engineering, the genome
itself will be modifiable, certainly at the somatic level and eventually at
the germ cell level.
It would be foolish to ignore the immense contribution of developmental and
environmental influences to the expression of complex behavior. In fact, most
human characters are complex, determined by the joint influence of many genes
and environmental stimuli, in a very poorly understood fashion. Intelligence
itself is polygenically determined, but that polygenic determinant accounts
only for about 50% of the variance in measures of intelligence across
populations. The other 50% is accounted for by the complex environmental
effects just alluded to. Similarly, complex human diseases such as
schizophrenia and endogenous depression may be characterized by polygenic
predispositions, but environmental triggering factors appear to be equally
important in producing symptomatology. In general, the nature of such
triggering stimuli is unknown.
Nevertheless, the next 100 years will see a complete understanding of,
therapeutic intervention in, and perhaps elimination from the gene pool of
those diseases that result from damage to single genes. Such diseases include
cystic fibrosis, adenosine deaminase deficiency, and Huntington's Chorea, to
name just a few that are currently known. Furthermore, diseases which involve
a relatively small set of molecular players, such as familial breast cancer,
will also yield to the new techniques of gene therapy. More speculatively, it
is reasonably likely that over the next century a molecular understanding will
be gained of the genetic underpinnings of most varieties of cancer, heart
disease, and perhaps the aging process itself.
There must be a point in this reductionist program where molecular biology
enters the domain of quantum physics, a point at which classical, Newtonian,
deterministic theory (the usually unacknowledged underpinning of modern
biology) must give way to quantum mechanical interpretation. Nowhere will this
be seen more clearly than in attempts to understand the mechanism and function
of the central nervous system and the diseases to which it is prone. Already,
quantum mechanical considerations are necessary in the modelling of
neurotransmitter receptor structure (Pardo et al., 1996). It is possible that
some of the "hard" problems in neurobiology, such as the nature,
origin, and development of conscious experience will require a quantum
perspective. The inevitable intersection of neurobiology with quantum
mechanics may lead to a twin understanding of cognition and the role of the
observer in quantum mechanics. That knowledge in turn will have profound
implications for psychiatric medicine, the definition of "human",
and perhaps the interpretation of physical reality itself. But to evaluate
such possibilities it is necessary to briefly consider both philosophical
approaches to the nature of consciousness and the essentials of quantum
mechanics. The difficulties in the interpretation of quantum mechanics (as
opposed to its pragmatic application) may provide unique insight into some of
the most difficult problems of neurobiology.
PHILOSOPHICAL HISTORY
Historical conceptions of the nature of consciousness have one extreme pole in
the idealism of Bishop Berkeley (Russell, 1967). Berkeley's idealism posited
that the only real things are minds and ideas. Being is perceiving. The
constancy of the physical world is attributed to a God who continually
perceives and never sleeps. The similarity of our perceptions of this world
follow from our partial participation in God's perceptions and, presumably,
mind. This is a kind of social solipsism. Reality is inherently consensual.
In contrast, Cartesian dualism admits to the existence of mind and matter.
Interestingly, Descartes himself did not take the position of what later
philosophers have called psychophysical parallelism; Descartes was an
interactionist, believing that mind and matter interacted at a specific
physical point. Since the pineal gland is a unitary structure in the brain, as
opposed to the hemispherically bilateral structures that are ubiquitous in the
central nervous system, Descartes assumed on geometrical grounds that the
solitary point of interaction had to be the pineal. This particular version of
interactionism was of course subsequently abandoned.
The rise of classical Newtonian mechanics negated any particular necessity
for an interactionist account. In fact, the Newtonian clockwork universe did
not require consciousness at all. Given a knowledge of initial conditions, it
was theoretically possible to predict all possible future states of the
universe by an application of the laws of mechanics and gravitation. Mind was
not excluded and could in principle maintain some kind of existence in
parallel to the workings of the body. But it was very easy to step from this
kind of psychophysical parallelism to the notion that mind is simply an
epiphenomenon of no functional utility.
Psychology at its origin still maintained a dualistic outlook. But
experimental difficulties in studying the contents of conscious thought, along
with the blooming of the logical positivist school, rapidly produced the
materialist outlook of Watson and ultimately Skinner in this country.
Psychology in this century has been dominated by the behaviorist outlook,
which is an essentially materialist tradition. This was not by any means a bad
outcome, since the tools necessary to objectively study the cerebral
correlates of conscious experience have only recently been developed. Such
imaging methodologies as magnetic resonance imaging and positron emission
tomography now allow the examination of the physiological substrate of
consciousness. In the absence of such tools, the Behaviorists developed useful
paradigms for the analysis of what was observable at that time, the behavior
of organisms.
INTERPRETATIONS OF QUANTUM
MECHANICS
But while the behavioral tradition was just beginning to flower, physics
itself went through a paradigm shift, first with the special and general
relativity of Einstein, then with the quantum mechanics of Bohr, Heisenberg
and others in the twenties and thirties (Baggott, 1994). In particular, the
essence of quantum mechanics is that particles of a sufficiently small size,
generally of atomic radius or smaller, can simultaneously exist in multiple
linearly superposed states, the sum of which is called a wave function. These
states can correspond to different positions, momenta, spin etc. Each state
evolves over time according to the Schrödinger equation in a completely
deterministic fashion. However, if an observation of the system is made, the
wave function collapses. That is, somehow the observation "selects"
a particular state (on the basis of its relative probability) and that state
corresponds to an exclusive classical alternative, i.e., a particularized
position, spin or whatever. All other states are excluded. That new state can
now evolve deterministically until the next observation. Thus quantum
mechanics incorporates an operation, collapse of the wave function (also
called reduction of the state vector where the state vector is the linear sum
of the complexly weighted possible alternative states) which is inherently
probabilistic, rather than deterministic in the classical Newtonian sense.
Furthermore, unlike the classical Newtonian picture (or even the relativistic
picture) of the universe, an observer is absolutely necessary (see, for
instance, Renninger's negative result, 1953 or the delayed choice experiment
of Wheeler, 1978, as cited in Cramer, 1986).
Nonetheless, various attempts have been made to dispense with the observer.
For instance, it has been suggested that all that is really required is a
measuring device to record the collapsed state. However, such a measuring
device is itself composed of subatomic particles. What then collapses the wave
function of the measuring device? If the answer is another measuring device,
this argument rapidly leads to an infinite regression of such devices. It has
also been suggested that measuring devices are inherently macroscopic and
considerations of wave function collapse do not apply at the macroscopic
level. However, there are numerous examples of quantum phenomena that do
indeed occur at the macroscopic level, including Bose-Einstein condensates
(Anderson et al., 1995), Penning-trapped individual ions (Steimle et al.,
1994)) and, most recently, spatial displacement of the superposed states of a
beryllium atom (Monroe et al., 1996). Furthermore, perhaps the best-known
gedankenexperiment in quantum mechanics, Schrödinger's famous Cat, is an
exploration of quantum phenomena at the macroscopic level. In this scenario, a
closed box contains a cat, minimally one radioactive atom, a Geiger counter,
and a device attached to the Geiger counter that will smash a vial of cyanide
gas if the counter registers the emission of one beta particle from the
radioactive atom. The probability of emission of the beta particle is 50%.
What is the state of the cat? If there were one hundred such boxes, the cat
would be alive in 50 and dead in 50. But for one such box, the Copenhagen
interpretation of quantum mechanics implies that the wave function of this
macroscopic cat is a superposition of two mutually exclusive states; the cat
is half dead and half alive. Notice that the apparatus has somehow converted
or amplified the wave function of the atom into the wave function of the cat
(this is often called macroscopic entanglement). But if an observer now opens
the box, the cat will be either dead or alive. The wave function has collapsed
to one state or the other as a result of that observation. So it appears that
it is possible to speak of both superposed states at the macroscopic level and
the observer-induced collapse of the associated macroscopic wave function.
Perhaps the most widely accepted attempt to evade the role of the observer
is Everett's Many Worlds model (Everett, 1957). In this interpretation, the
collapse of the wave function never occurs. Instead, at every possible choice
point, a new parallel universe buds off, corresponding to every possible
superposed state. Everett required that these universes be non-communicating.
Apparently communicating universes are logically equivalent to a megaverse in
which mutually exclusive alternatives could co-exist, much like the state(s)
of Schrödinger's Cat before the lid of the box is lifted. Furthermore, if
communication were allowed, then at least some of the possible allowed states
would include visitation of this particular world at this particular time by
travelers who would be quite willing to demonstrate their means of transit!
Since this has apparently not occurred, it would seem more likely that
Everett's Many Worlds are indeed non-communicating. However, this in turn
means that the theory is inherently untestable. One caveat here is that if a
traveler could attain velocities faster than light or if other means were
found for time travel into the past, then it would be possible (and probably
required to avert paradox) for the traveler to take a new path through the
Many Worlds.
At least two other models posit that wave function collapse does not occur.
Bohm's pilot wave theory (Bohm, 1952) suggests that the wave function is as
"real" as any other wave and determines the position of particles
according to the magnitude of a quantum potential. Unfortunately, this global
"hidden variables" theory makes predictions indistinguishable from
those of standard quantum theory, making it as difficult to test as Many
Worlds. More recently, quantum information theory (Cerf and Adami, 1996)
asserts that there are only waves, particles are illusory, and the wave
function does not collapse. It is not yet clear whether this theory is
falsifiable in the Popperian sense.
Other attempts allow wave function collapse, but avoid observer-induced
collapse. Such notions include Penrose's assumption (1991) that a future
theory of quantum gravity will provide such collapse without the necessity of
an observer, the hypothesis that the probability of wave function collapse
increases smoothly as a function of the total number of atoms comprising the
system (Ghiradi et al., 1986) and Cramer's interpretation (1986) that requires
a kind of virtual tachyon (advanced waves). A major problem for such
hypotheses are "delayed choice" experiments. In one cosmological
version of such an experiment, the wave function potentially can persist in
the superposed state for billions of years, until an observation is made
(Wheeler and Zurek, 1983). Thus the most accepted interpretation of quantum
mechanics does seem to require the observer. In particular, what is required
is a kind of measuring device with the capacity to collapse both the external
wave function as well as its own internal wave function (both consciousness of
externals and self-consciousness). Von Neumann (1955), Wigner (1961), and most
recently, Stapp (1993) have gone so far as to suggest that the apparent
collapse of the external wave function actually represents a collapse of
internal superposed brain states in the observer. It is argued here that that
capacity characterizes self-consciousness and that empirical test of the
observer interpretation may be possible.
The observer interpretation is not without difficulties. Strong
interpretation along the lines of von Neumann and Wigner suggest that
observers lacking in self-consciousness could not collapse the wave function.
At this point it is necessary to ask what species are likely to be
self-conscious. That in turn requires some empirical test of
self-consciousness. One such test actually exists (Oakley, 1985). It consists
of dabbing a spot of paint on the forehead of some test species and then
placing the subject in front of a mirror. If the subject then wipes the paint
spot off his head it may be inferred that he has identified the reflection in
the mirror with some sort of internal spatial map of his own body. This
ability to externalize the body image, to correlate the internal body image
point by point with an external reflection presupposes the concept "my
body" and the concept "me". This in turn suggests
self-reference and self-consciousness. Now this test is of course crude. One
could easily imagine organisms with a sense of self who simply think that the
mirror-reversed image is another entity. But this is the best that can
currently be done. It is interesting that chimpanzees, gorillas, and
apparently porpoises pass this test, but gibbons, orangutans, baboons and
other primates do not. The species that do pass the test seem to have some
rudimentary protolinguistic ability, as evidenced by the capacity for simple
two or three word sentences in sign language or other abstract modes of
communication. Perhaps the linguistic capacity makes it easier for a sense of
self to develop because it allows the explicit formulation of self-reference,
such as the cogito of Descartes (i.e., I think, therefore I am).
A THOUGHT EXPERIMENT
In any case, it may be asked whether a chimp can collapse the wave function,
as opposed to a dog. This is actually a doable experiment, without
asphyxiating cats or alarming the animal rights people. The dark-adapted
retina can detect a single photon, a quantum event (Baylor et al., 1979).
Imagine an apparatus that splits a pair of orbital electrons. The spin of the
first electron is registered by a device that converts the detection of the
electron spin into a single pixel on a monitor screen; red pixel for spin up,
blue pixel for spin down. The second electron is transposed to a similar
monitor 186,000 miles away. Well-trained chimps are placed in front of both
monitors. Each chimp has been conditioned to press either a lever for fruit
juice reward if she detects a point of red light, or a button for banana
pellet reward if she detects a blue dot on the monitor. If both colored lights
are simultaneously observed, the chimp throws a switch, which behavior is
rewarded with a sugar cube. Each chimp "simultaneously" observes the
remote screen. Now Pauli's Exclusion Principle states that orbital electrons
must have opposite spins. But the Schrödinger equation states that the wave
function of each electron is a superposition of the two opposite spin states,
up and down, before an observation takes place. If chimps can collapse the
wave function, then the pixels observed on the two monitors must be of
opposite colors to satisfy Pauli's requirement; if the first chimp sees red,
the second chimp must see blue and vice versa. What the chimps "see"
is inferred from whether they push the fruit juice lever or the banana pellet
button. If the chimps cannot collapse the wave function, then they may
"see" both colors simultaneously (the superposed spin states) and
both will throw the sugar-rewarded switch. That would provide a test of
whether both chimps are perceiving the ordinarily mutually exclusive
superposed uncollapsed states simultaneously. This procedure could be used to
determine whether any trainable species can collapse the wave function.
In this thought experiment there are two points to note. One is that the
wave function collapses instantaneously. If the spin of the first electron
were transmitted somehow to the second electron at the speed of light, there
would be a delay of at least one second before the monitor 186,000 miles away
registers the reciprocal spin of the second electron (in the case of true
"collapsers"). However, experimental data from Aspect (1982) and
other investigators show that the collapse is not limited by the speed of
light. One could object that the notion of simultaneity of observation is
disallowed by special relativity in any event, but in actual practice it is
feasible to separate the observations by a large enough distance to
demonstrate the instantaneous nature of the wave function collapse. This is
the essential non-local character of quantum mechanics, in some ways even more
unpalatable than the Newtonian notion of action at a distance, since this
constitutes instantaneous action at a distance! It is important to recognize
that this instantaneous transmission of an "influence" does not
imply the transmission of information at velocities faster than light; since
the collapse of the wave function of the first electron is random, the
collapse of the second wave function must also be observed to be random.
Another point is that the entire evaluation of the described experiment
would have to be done by a human observer after the fact. There is no
difficulty if chimps can indeed collapse the wave function. In that case a
human observer would note that if one chimp chooses the fruit juice button,
the other chimp chooses the banana pellet button; both chimps never push the
same button. But if chimps (or other species) cannot collapse the wave
function, there is an interpretational problem. It is instructive to consider
that the proposed experiment is an example of the famed Wigner's Friend
gedankenexperiment (1961). Here a second observer, Wigner's Friend, actually
opens Schrödinger's Box in the absence of Wigner.Wigner evaluates the state
of the cat by interrogating his friend. If his Friend is indeed a conscious
observer, the wave function collapsed at the time of the Friend's observation,
and Wigner's Friend simply tells Wigner whether the cat is alive or dead. But
if Wigner's Friend is not a conscious observer, then he is mathematically
equivalent to part of the "measuring instrument" that Wigner employs
post facto to determine the state of the cat. Wigner's observation of the
output of this "measuring instrument" collapses the wave function
into either dead cat or alive cat.
OBSERVATION OF THE SUPERPOSED
STATE
In the chimp experiment, shouldn't the human observer likewise collapse the
wave function, if the chimp is unable to do so? In that event, there should
never be an observation of a sugar-rewarded switch throw! Can a failure of
wave function collapse be observed even in principle? The answer, at least for
beryllium atoms, surprisingly appears to be yes (Monroe et al., 1996).
Superposition of states has been observed experimentally at the mesoscopic
level; that is, the level of a single isolated atom. So it is necessary to at
least provisionally conclude that the switch throw result is possible to
observe.
The observation of wave function collapse in this experiment would seem to
argue against the "no collapse" interpretations (see above).
However, all of the "no collapse" interpretations do allow apparent
or pseudo-collapses (for instance, Many Worlds suggests that an apparent
collapse in this universe to a particular state simply indicates a branch
point-all other states are attained simultaneously in corresponding
universes). Still the logical principle of Occam's Razor (i.e., "Entities
should not be multiplied unnecessarily.") argues against "no
collapse" models.
On the other hand, models that assume collapse without an observer could
possibly explain the beryllium atom experiment. The superposed state persisted
for some 20 microseconds; this might be the characteristic time to collapse at
this mesoscopic scale. However, the model of Ghiradi et al. (1986) predicts
the time to spontaneous collapse of the wave function of a single atom to be
100 million years; the model of Penrose (p. 340; 1994) predicts 10 billion
years! Perhaps other versions of spontaneous collapse could explain the
"quantum decoherence" (essentially synonymous with wave function
collapse) observed by Monroe et al. (1996). Alternatively, it may simply take
20 microseconds for an observer to collapse this particular superposed state
(perhaps an unlikely alternative since spontaneous collapse of the
corresponding brain state may take more than three orders of magnitude
longer-see below). It would be very interesting to know how long the
superposed state persists under unperturbed conditions; that is, without the
attempt to actually observe the superposition. Spontaneous collapse models
which posit quantum decoherence or the instability of quantum states entangled
with macroscopic states might predict that the state should still persist for
only 20 microseconds; the von Neumann/Wigner/Stapp interpretation would
suggest that the state could persist until the actual observation of
superposition is made. In addition, an intermediate result is possible; the
superposed state could have an intrinsic half-life, which is nonetheless
shortened by observation.
In addition to collapsing the wave function, can the observer in any
way influence the final collapsed state? What happens to the wave function if
the observer lies? More importantly, what happens if the observer
misperceives? It seems such possibilities must be considered if, as Stapp
suggests, the collapse is essentially a neural event in the brain of the
observer. Future neurophysiologists might well be able to induce a pattern of
neural activity corresponding to any desired visual perception in the brain of
a given subject. So when Schrödinger's box is opened, whether the cat is
observed to be dead or alive is entirely at the discretion of the
neurophysiologists. But then who is collapsing the wave function? The
neurophysiologists? The federal agency that funds the neurophysiologists?
Could the wave function "really" collapse to one result, even if it
is perceived to collapse to an opposite result? A positivist interpretation
would say this statement is without meaning; we are limited to the entirely
operational aspects of observation. But it appears that such an interpretation
of quantum mechanics must admit to the same consensuality of perception that
characterized Berkelian idealism. And this quandary does not result from some
possibly unrealizable advance in neurophysiology. Many experiments in social
psychology show that verbal report is very strongly influenced by social
factors. One famous experiment (Asch, 1958) involved a group of observers who
were asked to estimate the length of a line in a darkened room. All observers
but one were confederates of the psychologist who designed the experiment. The
confederates were enjoined to consistently over-or underestimate the length of
the yardstick. In about one third of the estimates the verbal report of the
true experimental subject matched the bogus estimations of the confederates.
It is impossible to know whether this particular experiment represented
compliancy on the part of the subject or a truly altered perception. But in
other experiments the social factor is clear. In a prototypical experiment a
confederate rushes into a crowded lecture hall, points a banana at the
lecturer and yells bang. The lecturer falls over backwards with a ketchup
stain spreading over his white shirt. Students after the fact report that they
saw a gunman shoot the professor (such experiments are discussed in Loftus,
1979). Just how many fingers did Winston Smith see in the interrogation scene
in Orwell's 1984? So there can be no doubt that the perception of the observer
is malleable. This implies that observer-induced collapse of the wave function
must be malleable and subject to all the influences of social psychology.
However, a realist interpretation would say that the wave function
collapses to a particularized state no matter what the observer may perceive.
In this case, the observer institutes collapse, but can have no effect, no
matter how small, on the final state to which the wave function collapses. If
this were not the case, then in the chimp experiment (see above) the
manipulation of one chimp's sensory experience (a bias toward the perception
of one spin state or another) would influence the collapsed spin state
observed by that chimp, as well as the reciprocal spin state observed by the
second chimp. This paradigm could then be employed to send information at a
velocity greater than that of light, contradicting the central tenet of
special relativity (see above). This contradiction and the lack of any
experimental evidence that the observer can influence in any way the final
state of the wave function collapse suggests that the realist interpretation
(see above) may be correct. But absence of evidence is not evidence of
absence! It is not at all clear that the realist view of collapse without
observer influence (other than to precipitate the collapse) is any more
verifiable than the hidden variable theories which constitute another form of
realist interpretation. In fact, yet another variant on Wigner's Friend can be
imagined. Assume both a neurally controlled observer and fifty
"uncontrolled" observers who all observe a series of openings of
Schrödinger cat boxes. The controlled observer's perceptions are manipulated
so as to produce an outcome of 50 dead and 50 live cats over a series of 100
observations. The uncontrolled observers should observe the same cumulative
percentages. However, the expectation is that all uncontrolled observers will
agree on the outcome of any individual box opening. In contrast, the
controlled observer will agree with the other observers only 50% of the time.
Is this evidence for a realist interpretation, a reality at variance with the
controlled perceptions of the individual observer? But what if the 50
observers are actually the ones who are controlled and the single observer is
the uncontrolled observer (much like the Asch experiment, see above)? The
point is that without prior knowledge of the various factors which influence
perception, we cannot know which outcome represents "reality"; all
we have is a majority opinion. In general, such prior knowledge is not
available. From an operational standpoint, then, a majority opinion might as
well represent reality as consensual delusion.
It is still possible to ask the question, "What was the state of the
universe before there was a social psychology; that is, let's say two million
years ago before the advent of self-conscious primates?" Now one answer
to this is that the universe was in an uncollapsed superposition of all
possible states. Tipler's Strong Anthropic Principle (Tipler, 1986) suggests
that the physical constants of the universe have the values they have because
they resulted from an evolutionary process that produced self-conscious
observers who in turn collapsed the wave function to just that alternative
state associated with those particular physical constants conducive to the
existence of self-conscious observers. But even in this "just so"
story there is no reason to conclude that higher primates (and perhaps
cetaceans) are the only self-conscious organisms in the universe. In fact,
this argument may actually be used to infer the existence of extra-terrestrial
intelligences capable of collapsing the wave function billions of years before
the condensation of the earth from the solar nebula.
POTENTIAL APPLICATION TO
NEUROBIOLOGY
So it appears that an observer interpretation of quantum mechanics is
plausible (although it does lead to teleological peculiarities). More
importantly, and unlike the other interpretations discussed, it is testable.
But what does all this have to do with neurobiology?
To begin to answer that question it is first necessary to ask what possible
neural machinery could collapse the wave function? One answer is given by
Henry Stapp (1993). It is plausible that an extremely large, perhaps infinite,
number of neural states are simultaneously superposed on the cellular hardware
of the brain. Each of these superposed neural states represents some possible
perception of the external world. Consciousness selects one of these internal
states as reality; this is synonymous with collapse of the wave function to
one of the superposed neural states. That collapsed neural state encompasses
the observer-induced collapse of the external wave function. That neural state
is also the state that necessarily allows and empowers self-consciousness in a
recursive fashion.
What is this conscious state? Many, if not most, neuroscientists treat
consciousness metaphorically as a kind of distributed software program that
runs on the hardware of the central nervous system. While it is possible to
reduce a high level computer program to a series of ones and zeros in machine
language, it is much easier to understand a program at the level of the
programming language, as long as the particular language employed is known.
The project of the neurophysiologist is to attain an understanding of
internal, subjective experience, the "feel" of subjectivity, the
conscious experience of the color purple, for instance, by interpreting this
experience in terms of the machine language of the firing of neuronal
networks. This is sometimes referred to as the binding problem. The equally
difficult problem for the traditional cognitive psychologist is to understand
the programming language of the "other" based primarily on a
knowledge of her own internal language, some hope that that language of
internal experience does not differ too much from that of the
"other", and perhaps some general rules of thumb based on the last
100 years of psychological endeavor. Both of these projects seem much more
realizable with the recent advent of brain imaging techniques. It is now
possible to visualize the activation of specific brain areas during cognitive
acts. With very few exceptions the activated regions are cortical regions.
The greatest evolutionary advance of primates and, to a lesser extent,
mammals in general, has been a tremendous increase in cortical surface area in
comparison with non-mammalian species. Certain regions of cortex in particular
are greatly elaborated in the greater apes and in man. Chief among them are
the temporal cortical regions involved in the generation and comprehension of
language and the frontal regions, particularly prefrontal cortex, which seem
to be essential for such tasks as decision making, and strategic planning.
Conscious function appears to be distributed very widely over cortical areas.
Localized brain damage rarely affects the sense of self; only in those
diseases in which there is massive cortical destruction or loss of cortical
activating input (e.g., Alzheimer's, Parkinson's; Perry and Perry, 1995) is
there seen an apparent loss of that sense of self (It would be interesting to
employ the "mirror test", Oakley, 1985, in such patients).
Remarkably, in Parkinson's Disease some reversibility can be observed. In the
1950s when the l-dopa treatment was first employed (Sacks, 1983),
institutionalized patients were able to move and speak for the first time in
decades, in some cases for the first time in 40 years. One of the biggest
difficulties with such patients was making them understand just how much time
had passed. These patients were unwilling time travelers into the future. When
asked where his mind was for the long period before l-dopa treatment, one
patient responded that it was as if he had been inhabiting a black hole. In
spite of the vividness of this metaphor, the patient may have experienced a
loss of memory for the prior state, rather than a lack of conscious experience
at that time (although memory and consciousness have much in common; see
below). But there is another reversible loss of consciousness; the slow wave,
non-dreaming sleep humans experience every night. Once again, in this state
there is a great reduction in cortical electrical activity, and an absence of
conscious experience (as opposed to rapid eye movement or dream sleep, in
which there is a restoration of cortical activity and at least some, albeit
fragmented, cognitive experience). But every morning on awakening the same
self is perceived that retired the previous night (although it is not possible
to remember the precise moment of sleep). Similarly, occasionally individuals
recover from long-lasting coma, experiencing no change in this sense of self.
Such considerations suggest that consciousness is global, stored as some
kind of permanent record, and dependent only for activation (booting up?) on
some immediate pattern of electrical activity in the brain. Such properties
are also characteristic of memory. Long term storage of memory depends on
molecular modification in the brain; the reading out of new patterns in
messenger RNA and the conversion of that message into newly synthesized
protein. The laying down of such records in the course of maturation and
learning is often under conscious direction and control, altering the
consciousness that is doing the learning. In this sense consciousness is a
self-programming program. But if the capacity for laying down memory,
consolidation, is lost, consciousness is stuck in whatever state it was in
when the consolidation mechanism was damaged. Thus Sachs (1990) reports a
patient with such damage whose consciousness is locked in 1945; no possible
experience can move his self from that particular temporal frame.
Is it possible to localize sub-programs of consciousness in particular
areas? Available evidence suggests that this is so. Various areas of cortex
are necessary for conscious auditory, visual, and somatic perception. Other
regions are necessary for fine motor control. Wernicke's area in the left
temporal lobe is absolutely necessary for language (at least in right-handed
males). Undoubtedly such a cortical capacity for language sharpens our sense
of self, but it is unlikely that it is essential for self-consciousness. Many
aspects of conscious experience appear to be non-verbal. The split-brain
experiments of Sperry, Gazzaniga and others (summarized in Gazzaniga et al.,
1970) showed that the right hemisphere, the non-speech hemisphere, is
conscious even though it lacks access to the speech centers of the left
hemisphere because the connecting fibers have been cut as a treatment for
intractable epilepsy. In fact, using non-verbal communication procedures, one
patient was shown to have motivationally different life goals dependent on
which hemisphere was queried (Gazzaniga et al., 1977); this suggests that
consciousness can not only persist in a hemisphere disconnected from the
speech centers, but actually evolve and change in the way that hemispherically
integrated selves seem to do.
Although consciousness appears to be global, is it possible that the neural
mechanism responsible for collapsing the wave function is localized? If so,
the obvious place to look is prefrontal cortex, the phylogenetically youngest
cortical area. One of the earliest documented cases of prefrontal lesion in
humans was the case of Phineas Gage. Gage was a miner who managed to propel a
blasting rod through his jaw and out the frontal portion of his skull,
effectively destroying his prefrontal cortex. From that point onward, Gage
lost the capacity for decisiveness, could no longer function as a foreman, and
seemed to lack the self-censoring function that Freud referred to as
super-ego. Is it possible that Gage lost the capacity to collapse the wave
function and from that point on functioned only as a kind of robot on the
stage of human affairs? Certainly experimental lesion data in non-human
primates suggest strongly that prefrontal cortex is necessary for tasks
involving choice, particularly choices that are separated in time (delayed
response, delayed alternation; Warren and Akert, 1964). One way of describing
this deficit is to call it a deficit in strategic planning; the application of
past memory to future choice.
Available genetic data suggest that the uniqueness of the human species in
comparison to the chimpanzee boils down to about 600 quintessentially human
genes, not present in chimps (this calculation assumes 98% identity between
human and chimp genomes (Luke and Verma, 1995) and about 30,000 genes in the
human central nervous system (Sutcliffe et al. 1983). The prefrontal cortex
(and probably temporal cortex) would seem to be particularly good places to
look for the activation of such genes. In fact, new molecular techniques such
as differential display will soon be used to define that suite of specifically
human genes and, by implication, perhaps humanity itself. It is possible that
one such gene could code for a protein rich in the prefrontal cortex that is
essential for the observer's ability to collapse the wave function, a function
that might very well subjectively feel like conscious choice. In fact an
entire cascade of such proteins could be the substrate of wave function
collapse. Hypothetical wave function collapsing proteins will be referred to
here as collapsins.
But there are more constraints that can be placed on this neural model of
wave function collapse. If the conservative assumption is made that neural
superposed states will eventually spontaneously collapse, even in the absence
of observation, then it is possible to calculate that a sub-neuronal region
with a radius of one micron could persist for a period of not more than 50
milliseconds in a superposition of states, before irrevocable collapse of the
wave function (Penrose, 1994). The argument reflects the inevitable
entanglement of the superposed states with surrounding macroscopic states. So
there are two boundaries in the neuronal regime; the spatial one corresponds
to sub-neuronal dimensions, the temporal one is in the same domain as many
neuronal processes and comparable (within a factor of two) to the latency at
which a visual stimulus maximally disrupts visual iconic memory (25 msec;
Weisstein and Haber, 1965). Such disruption could reflect the instability of a
superposed neural wave function near the point of spontaneous collapse.
Furthermore, if iconic memory exemplifies the shortest possible
cognitive/perceptual event, such considerations suggest that thought itself
could be quantized, as was anticipated over forty years ago (successive
sensory stimuli will interfere only if they occur within the same
"quantum of psychological time"-Stroud, 1955). It is perhaps no
coincidence that the reciprocal of this time interval (40 Hz) is the frequency
of a magnetoencephalographic oscillation that has been proposed to bind
fragmentary sensation/discrete neuronal activity into unitary conscious
experience (Llinas and Ribary, 1993).
What sub-neuronal process could possibly meet the hypothesized spatial and
temporal criteria just discussed? Penrose (1994) suggests microtubules, the
structural support network of cells. But microtubules are ubiquitous in all
cells. Wave function collapse might then be initiated by paramecia, a prospect
perhaps acceptable to Heisenberg, but not to most neurobiologists!
Are there specifically neural mechanisms that could operate under these
spatio-temporal constraints? There are at least three (Ghosh et al., 1995).
The first is the mechanism by which calcium ions enter a terminal bouton and
effect the release of a synaptic vesicle, filled with a neurotransmitter, into
the synaptic cleft. Stapp (1993) calculates that the effective wave function
of a calcium ion is much larger than its classical radius, making this process
of transmitter release one in which superposition of many ionic states is
possible. The actual release of the contents of a vesicle may require just
four calcium ions, probably well within the quantum regime (Heidelberger et
al., 1994). A second possibility is the binding of the neurotransmitter with
the receptor on the postsynaptic membrane. Although release of transmitter may
be a quantum event, the effect of receptor occupation is probably a classical
process. Each vesicle discharges about 5000 molecules of transmitter into the
synaptic cleft (e.g., Hartzell et al., 1976), and the smallest transmitter has
a molecular weight of about 200. So this is the rough quantum equivalent of
perhaps a million protons, surely well within the classical regime.
Furthermore, to produce any macroscopic response, many receptors may require
occupation. So even if transmitter release is a quantum event, the effect of
that transmitter can be treated in classical terms, and typically is according
to the laws of statistical thermodynamics. However, although an interruption
in neurotransmission may disrupt the expression of consciousness (e.g., as in
slow wave sleep), the molecular "record" of consciousness somehow
persists, even after many years in coma. What is required is a means of
altering that record. Thus, a third mechanism, based on the action of
intracellular calcium, may have all the characteristics of the quantum regime
and in addition be relevant to the process of molecular registration that
would seem to underly conscious experience. In fact, this mechanism is very
often the effector or final common path for the first two mechanisms
considered, largely because intracellular enzymes are generally
calcium-dependent. So intracellular calcium is a focal point for all the
neuronal events that transpire after the occupation of postsynaptic receptors
by neurotransmitter molecules.
Calcium-activated calcium release is an intracellular mechanism that
magnifies the activity of as little as one calcium ion. Consider the possible
effect of a single calcium ion entering the neuron through a voltage or
neurotransmitter-gated calcium channel. If that calcium ion encounters a
ryanodine receptor-gated pool of calcium it can facilitate the further release
of calcium from that pool in a positive feedback-mediated exponential process
within about 50 milliseconds (Monck et al., 1994) [Footnote1].
The result is calcium "hot spots" which are easily visualized in
individual neurons (Figure
1A, B). That exponential rise in calcium may easily achieve a classical
local concentration and thus constitute the molecular basis of the wave
function collapse. The amplification involved may be as much as three to four
orders of magnitude, a kind of inflationary "little bang" in the
internal spacetime of the neuron [Footnote
2]. Furthermore, at least two immediate sequelae are apparent. Calcium
ions bind to certain proteins (calcium binding proteins such as calmodulin) to
form molecular complexes which can be translocated to the nucleus to initiate
genetic transcription, leaving a molecular record or memory of the event.
Secondly, the molecular complex may also activate a calcium/calmodulin-dependent
protein kinase which can then phosphorylate the calcium channel which admitted
the initial calcium ion which initiated the intracellular wave function
collapse. Phosphorylation may alter the opening time or probability of opening
of the calcium channel. Thus the amplitudes of the next superposed set of
states can be affected by structural changes in the calcium channel, which
will alter the probability that a calcium ion can pass through the channel and
initiate another round of wave function collapse. Furthermore, still other
transcriptional and translational events in the nucleus, touched off by the
exponential rise in calcium, may also ultimately alter the amplitudes of
certain of the superposed states in the next quantum round, affecting the
probability of collapse to a subsequent macroscopic state. In essence, this
influence of the prior macroscopic substrate of memory on the next macroscopic
state may produce the phenomenon of continuity of consciousness.
|
|
| Figure 1:This figure shows a rat
Purkinje cell in primary culture. Subsequent to loading with Fura-2AM
(3 uM for 25 min in 5% CO2 at 36 degrees C.), the culture
was equilibrated at room temperature for 35 minutes in artificial CSF.
The culture was then utilized for calcium imaging. Relative intensity
of intracellular calcium is indicated on the vertical scale bar, with
red to white indicating the highest concentration (approximately 1 uM).
The horizontal scale bar=50 um. Used with permission from Howard
Strahlendorf, 1996. |
|
|
| Figure 2: (top) This figure is a
magnification of the extensive, probably axonal, process in Figure 1.
This frame is taken subsequent to glutamate administration (10 uM).
Note red calcium "hot spots" along the process, in response
to glutamate-induced depolarization. (bottom) Same process, 50 msec
later. Note disappearance of "hot spots". Vertical intensity
scale bar as in Figure 1. Horizontal scale bar=25 um. |
Assuming roughly spherical neurons with average diameters of 20 microns and
perhaps 10 billion such neurons in the human brain, 10 trillion calcium hot
spot "collapses" could occur every 25 msec. If 10 % of these events
occur in relevant cortical areas, what mechanism could possibly synchronize
the collapse of some trillion such wave functions in the requisite time
interval? If uncollapsed superposed wave functions (the U state) alternate in
time with collapsed or reduced states (the R state), the alternation can be
considered an oscillation with a frequency of perhaps 40 Hz (see above). But
very early in cognitive development, the U-R oscillations might vary in phase
and period. Still, in a coupled multi-oscillator population, the shortest
period oscillator will eventually synchronize and drive the remainder of the
oscillator population. If 25 msec is indeed the shortest period of a cognitive
event, then a global 40 Hz oscillation should eventually dominate (as seems to
be the case in those arousal states (waking and rapid eye movement sleep, but
not slow wave sleep) in which some form of cognitive activity is possible;
Llinas and Ribary, 1993). It would be most interesting to determine if the
appearance of the 40 Hz oscillation is correlated with cognitive development
in humans.
But even if the calcium collapses are synchronized throughout cortex, the
ultimate R states are random (more properly, determined by the probabilities
or squared amplitudes of the states making up the U wave function). The unity
of conscious experience suggests that the trillion or so R states occurring
each 25 msec must be in some sense compatible. One way to provide such
compatibility or global coherence would require that the calcium hot spots
behave very much like a Bose-Einstein condensate. Such condensates result when
an aggregate (potentially macroscopic) population of atoms are forced into the
same quantum mechanical state (Anderson et al., 1995). Similar coherent states
may occur in biological systems (Fröhlich, 1975; Pribram,1975; Marshall,
1989; Penrose, 1994).
The 40 Hz oscillation in a globally coherent cortical U-R transition could
be the signature of the self-conscious observer. The oscillation is both a
product of and modifier of the brain states, produced by collapse of the wave
function, which enable conscious experience. The 40 Hz oscillation emerges
from, but also synchronizes the coherent U-R transition in an objective
fashion (a kind of self-organization). At the same time the identification of
the 25 msec collapse with the minimal perceptual event potentially preserves
the observer-induced collapse interpretation of quantum mechanics at the
neural level. Thus, this interpretation is compatible with the hypothesis of
Stapp (1993) and simultaneously similar to the hypothesis of
"orchestrated objective reduction" of the wave function (Penrose,
1994; Hameroff and Penrose, 1996)[Footnote
3].
What all this condenses to is the hypothesis that the neural substrate for
collapse of the wave function is most likely in the phylogenetically new
neocortex, perhaps prefrontal cortex. Furthermore, the various spatio-temporal
constraints suggest that calcium-activated calcium release could be the
mechanism of wave function collapse. The molecules most likely to influence
this collapse, previously referred to as collapsins, are likely to be calcium
binding proteins or calcium-dependent kinases specific to the prefrontal
cortex in homo sapiens and perhaps one or two other mammalian species.
Isoforms of these molecular entities (kinases, calcium binding proteins) are
indeed distributed in the frontal and prefrontal cortex in a species-specific
fashion, so unique human variants are a strong possibility (Picciotto et al.,
1993; Stein et al., 1992). While this model employs a particular
neuron-specific mechanism, in contrast to microtubule models (e.g., Penrose,
1994; Hameroff and Penrose, 1996), it is certainly possible that other neural
structures could constitute the substrate of wave function collapse.
IMPLICATIONS FOR PSYCHIATRY AND
NEUROLOGY
What are the implications of neurally-mediated wave function collapse with
regard to neuropathology? First, if there is any truth to this hypothesis, it
will force a re-examination of certain cherished observations in neurology.
For instance, Penfield and Jasper (1954) observed that electrical stimulation
of regions of the human temporal lobe prior to temporal resection for
intractable epilepsy caused the activation of vivid memory-like subjective
experiences in the patient. Such perceptual experience was superimposed on the
environment of the operating theatre and sometimes indistinguishable in terms
of salience from that "real" environment. This "doubling"
of perceptual experience has also been noted at the initiation of temporal
lobe seizures in some patients. Is it possible that such patients are indeed
experiencing a superposition of neural states? Is it possible that other vivid
perceptual conditions such as hallucinations, waking reverie, and lucid
dreaming all reflect linear superposition of what are essentially quantum
neural states? Certainly in the epileptic state and perhaps in other
conditions the 40 Hz U-R transition frequency may be disrupted by seizure
activity. If so, wave function collapse may be disturbed or even prevented. In
these cases it is clear that external observers do not perceive the
"doubling", perhaps because they are part and parcel of the
consensus view that such experiences are necessarily personal.
Very little is known of the neural substrates of psychotic states. It is
known that certain schizophrenics often experience disembodied auditory
hallucinations, "hearing voices". This particular symptom is most
rapidly extinguished by antipsychotic drugs, which antagonize dopamine
receptors. It is also known that the generation, perception, and understanding
of language is organized in the temporal lobe, which also receives a
substantial dopamine innervation in humans (cingulate cortex also receives a
substantial dopamine innervation and is activated, along with temporal lobe
structures, in schizophrenic auditory hallucinations; Silbersweig et al.,
1995; McGuire et al., 1993). Is it possible that schizophrenia is a quantum
disease, a failure of quantum coherence which allows autonomous collapse of a
local temporal lobe wave function at variance with the global cortical
collapse that is interpreted as ordinary consciousness? This would be
identical to a regional phase difference in the 40 Hz U-R frequency. Is it
possible that such quantum decoherence could result in the subjective
perception of what seem to be externalized voices or other people's thoughts,
as patients sometimes describe the schizophrenic experience? This kind of
"splitting" of the wave function into two distinct classical states
(two observers?) contrasts with advanced Parkinson's Disease (characterized by
a reduction in dopamine transmission), in which there is no wave function
collapse because there is no consciousness.
Another potential quantum neurological disease is multiple personality
disorder (MPD). If the squared amplitudes of various superposed states within
the quantum wave function are similar in magnitude, there may be near-equal
probabilities of collapse into distinct macroscopic states, i.e., multiple
personalities. If ongoing continuity of consciousness represents serial
collapse of the wave function into macroscopic neural states which are always
similar to preceding states, then MPD may represent alternating collapse into
distinct quasi-stable neural states. In this disorder, the personalities
dominate behavior serially, as control passes from one personality to the
next, rather than the parallel struggle for dominance in paranoid
schizophrenia (the individual ego vs. the compulsions of the externalized
"voices"). In fact, the EEG can exhibit considerable variation as
different personalities dominate in MPD (Cocker et al., 1994); in contrast,
the EEG is much more stable in schizophrenic episodes.
Today dopamine receptor blockers are administered to reduce functional
dopamine hyperactivity in schizophrenia-the net result may be reestablishment
of global neural quantum coherence. For MPD, the therapeutic goal is to
integrate the various personalities into a single dominant personality-this in
turn sounds very much like establishing a maximally probable state (highest
squared amplitude) for macroscopic collapse of the neural wave function. It is
possible that a detailed theory of quantum neurophysiology would allow the
determination and perhaps even modulation of superposed state amplitudes in
the normal condition and in pathological conditions such as MPD. Furthermore,
such a theory might allow an explanation of the means by which excessive
dopamine transmission might lead to a failure of quantum coherence and
subsequent schizophrenic symptomatology. Both of these diseases have proved
refractory to any kind of classical mechanistic interpretation; perhaps a
quantum interpretation would be therapeutically useful.
CONCLUSION
It is clear that neurobiological investigations are approaching the size
domain at which quantum effects may be predicted. Certain interpretations of
quantum mechanics are now proving testable. Already, some of the simplest
models of spontaneous wave function collapse have apparently been falsified
(Monroe et al., 1996). Observer interpretations of wave function collapse are
likewise testable. If such interpretations prove correct, the neural substrate
of wave function collapse will require investigation. It has been suggested
here that the substrate of collapse may well be calcium-activated calcium
release in cortical regions. Such a mechanism could well constitute the
substrate of collapse even if such collapse is spontaneous and purely
objective, rather than observer-induced.
In any event, modern molecular techniques will lead to the specification of
a suite of genes in the central nervous system that are uniquely human in
nature. Among these genes may be found the hypothetical collapsin genes.
Various tests could be used to verify their presence and function. Such genes
should be highly expressed in neocortical regions, particularly temporal and
prefrontal cortex. Such genes should be absent in non-primate species and
perhaps weakly expressed in chimps and gorillas. Such genes might be
inactivated in slow wave sleep, coma, Parkinson's Disease, and Alzheimer's
Disease, but perhaps highly expressed in delusional states. At least three
varieties of quantum psychiatric disorders may be possible: 1) failure of
collapse, as in the "doubling" of perception in temporal lobe
epilepsy 2) failure of quantum coherence, as in paranoid schizophrenia 3)
collapse into low probability states, as in MPD. The first and second
varieties, but probably not the third, may be associated with amplitude and
phase differences in the 40 Hz U-R transition frequency. The interpretation of
neuropsychiatric disease in quantum terms could mark a revolutionary
alteration in our views of consciousness and brain function.
ACKNOWLEDGMENTS
This work was supported in part by NIA grant PO1 AG11084. The author is
indebted to Howard Strahlendorf, Thomas Tenner and Louis Chiodo for helpful
suggestions.
FOOTNOTES
Footnote 1. Another exponential
process like this could involve sodium-dependent action potentials. It is
possible that the entry of a single sodium ion could depolarize the membrane
enough to admit more sodium ions, causing more depolarization etc. in a
runaway process, producing the action potential as a collapsed macroscopic
event. Unlike the simpler model of calcium-activated calcium release, this
process imposes the additional constraint that the neuron be at firing
threshold. It is possible to construct a scenario much like Schrödinger's
Cat, in which a quantum event can elicit a macroscopic collapse, in this case,
an action potential, but that does not imply that any large number of neurons
just happen to be at threshold at any given time or that the nervous system
operates in this fashion.
Footnote 2. For a volume of
approximately 0.5 micron radius (compare to the 20 micron radius of large
neurons) and a basal free intracellular calcium level of 100 nM, it is easily
shown that 50-100 calcium ions, a number comfortably in the quantum regime,
may occupy this region that will become the "hot spot". Once a
calcium ion comes into contact with a ryanodine receptor associated with a
bound pool of calcium, the exponential process of calcium-activated calcium
release can produce a calcium concentration in approximately the same volume
corresponding to 100,000 or more calcium ions, all in a time frame of 50
milliseconds. These numbers are in remarkable agreement with the constraints
on quantum coherence recently suggested by Penrose (1994).
Footnote 3. It is also possible that
observer-induced collapse is illusory, reflecting the fact that the minimum
percept duration must necessarily equal the duration of a U-R interval,
creating the impression that observation induces collapse, as opposed to
objective collapse determining the minimum duration of unitary perceptual
events. However, this scenario would not explain the failure to see the 40 Hz
frequency in slow wave sleep (Llinas and Ribary, 1993), if indeed that
frequency is the frequency of U-R transition. As long as some sensory stimuli
continue to impinge on the nervous system, objective reduction should
continue, even in the absence of conscious perception. The failure to see the
40 Hz frequency suggests instead that conscious perception may be intimately
associated with the U-R transition.
REFERENCES
Anderson, M. H., Ensher, J. R., Matthews, M. R., Wieman, C. E., and Cornell,
E. A. (1995) Observation of Bose-Einstein consdensation in a dilute atomic
vapor. Science, 269: 198-201.
Asch, S. E. (1958) Effects of group pressure on the modification and
distortion of judgments. In: Readings in Social Psychology, E. E. Maccoby, T.
M. Newcomb, and E. L. Hartley, eds., Holt, Rinehart and Winston, New York, pp.
174-183.
Aspect, A., Dalibard, J., and Gerard, R. (1982) Experimental tests of
Bell's inequalities using time-varying analyzers. Physical Review Letters, 49:
1804.
Baggott, J. The Meaning of Quantum Theory. (1994) Oxford University Press,
New York.
Baylor, D. A., Lamb, T. D., and Yau, K. W. (1979) Responses of retinal rods
to single photons. Journal of Physiology, 288: 613-634.
Bohm, D. (1952) A suggested interpretation of the quantum theory in terms
of 'hidden' variables, I and II. Physical Review, 85: 166.
Cerf, N. J., and Adami, N. J. (1996) Quantum mechanics of measurement.
e-print Archives, quantum-ph/9605002.
Cocker, K. I., Edwards, G. A., Anderson, J. W., and Meares, R. A. (1994)
Electrophysiological changes under hypnosis in multiple personality disorder:
A two-case exploratory study, Australian Journal of Clinical and Experimental
Hypnosis, 22: 165-176.
Cramer, J. G. (1986) The transactional interpretation of quantum mechanics.
Reviews of Modern Physics, 58: 647-687.
Everett, H. (1957) 'Relative state' formulation of quantum mechanics.
Reviews of Modern Physic, 29: 454.
Fröhlich, H. (1975) The extraordinary dielectric properties of biological
materials and the action of enzymes. Proceedings of the National Academy of
Sciences, 72: 4211-4215.
Gazzaniga, M. S. (1970) The Bisected Brain. Appleton-Century-Crofts, New
York.
Gazzaniga, M. S., LeDoux, J. E., and Wilson, D. H. (1977) Language, praxis,
and the right hemisphere: clues to some mechanisms of consciousness.
Neurology, 27: 1144-1147.
Ghiradi, G. C., Rimini, A., and Weber, T. (1986) Unified dynamics for
microscopic and macroscopic systems. Physical Review D, 34: 470.
Ghosh, A., and Greenberg, M. E. (1995) Calcium signalling in neurons:
molecular mechanisms and cellular consequences. Science, 268: 239-247.
Hameroff, S. R. , and Penrose, R. (1996) Conscious events as orchestrated
spacetime selections. Journal of Consciousness Studies, 3: 36-53.
Hartzell, H. C., Kuffler, S. W., and Yoshikami, D. (1976) The number of
acetylcholine molecules in a quantum and the interaction between quanta at the
subsynaptic membrane of the skeletal neuromuscular synapse. Cold Spring Harbor
Symposium on Qunatitative Biology, 40: 175-186.
Heidelberger, R., Heinemann, C., Neher, E., and Matthews, G. (1994) Calcium
dependence of the rate of exocytosis in a synaptic terminal. Nature, 371:
513-515.
Llinas, R., and Ribary, U. (1993) Coherent 40 Hz oscillation characterizes
dream state in humans. Proceedings of the National Academy of Sciences, 90:
2078-2081.
Loftus, E. (1979) The malleability of human memory. American Scientist, 67:
312-320.
Luke, S. and Verma, R. S. (1995) Human (Homo sapiens) and chimpanzee (Pan
troglodytes) share similar ancestral centromeric alpha satellite DNA sequences
but other fractions of heterochromatin differ considerably. American Journal
of Physical Anthropology, 96: 63-71.
Marshall, I. N. (1989) Consciousness and Bose-Einstein condensates. New
Ideas in Psychology, 7: 73-83.
McGuire, P. K., Shah, G. M., and Murray, R. M. (1993) Increased blood flow
in Broca's area during auditory hallucinations in schizophrenia. Lancet, 342:
703-706.
Monck, J. R., Robinson, I. M., Escobar, A. L., Vergara, J. L., and
Fernandez, J. M. (1994) Pulsed laser imaging of rapid Ca2+ gradients in
excitable cells. Biophysical Journal, 67: 505-514.
Monroe, C., Meekhoff, D. M., King, B. E., and Wineland, D. J. (1996) A
"Schrödinger Cat" superposition state of an atom. Science, 272:
1131-1136.
Oakley, D. A. (ed.) (1985) Brain and Mind. Methuen, London.
Pardo, L., Batlle, M., Dunach, M., and Weinstein, H. (1996) Structure and
activity of membrane receptors: Modeling and computational simulation of
ligand recognition in a three-dimensional model of the 5-hydroxytryptamine1A
receptor. Journal of Biomedical Science, 3: 98-107.
Penfield, W. and Jasper, H. H. (1954) Epilepsy and the Functional Anatomy
of the Human Brain. Little, Brown, Boston.
Penrose, R. Shadows of the Mind. (1994) Oxford University Press, New York.
Penrose, R. (1991) The Emperor's New Mind. Penguin Books, New York.
Perry, E. K., and Perry, R. H. (1995) Acetylcholine and hallucinations:
disease-related compared to drug-induced alterations in human consciousness.
Brain and Cognition, 28: 240-258.
Picciotto, M. R., Czernik, and Nairn, A. C. (1993) Calcium/calmodulin-dependent
protein kinase I. cDNA cloning and identification of autophosphorylation site.
Journal of Biological Chemistry, 268: 26512-26521.
Pribram, K. H. (1975) Toward a holonomic theory of perception. In:
Gestalttheorie in der Modern Psychologie, S. Ertel, ed., pp. 161-184, Erich
Wengenroth, Köln.
Russell, B. (1967) The Problems of Philosophy. Oxford University Press,
London.
Sacks, O. (1983) Awakenings. Dutton, New York.
Sacks, O. (1990) The Man Who Mistook His Wife for a Hat. Harper Perennial,
New York, pp. 23-42.
Silbersweig, D. A., Stern, E., Frith, C., Cahill, C., Holmes, A., Grootoonk,
S., Seaward, J., McKenna, P., Chua, S. E., Schnoor, L., et al. A functional
neuroanatomy of hallucinations in schizophrenia. (1995) Nature, 378: 176-179.
Stapp, H. P. (1993) Mind, Matter and Quantum Mechanics. Springer-Verlag,
New York.
Steimle, T., Alber, G., and Briggs, J. S. (1994) Quantum dynamics of a
charged particle in a Penning trap. Zeitschrift fur Physik D, Atoms, molecules
and clusters, 29: 21.
Stein, M. B., Padua, R. A., Nagy, J. I. , and Geiger, J. D. (1992) High
affinity [3H] ryanodine binding sites in postmortem human brain: regional
distribution and effects of calcium, magnesium, and caffeine. Brain Research,
585: 349-354.
Sutcliffe, J. G., Milner, R. J., Shinnick, T. M., and Bloom, F. E. (1983)
Identifying the protein products of brain-specific genes with antibodies to
chemically synthesized peptides. Cell, 33: 671-682.
Stroud, J. (1955) The fine structure of psychological time. In: Information
Theory in Psychology, H. Quastler, ed., Free Press, New York.
Tipler, F. J., and Barrow, J. D. (1986) The Anthropic Cosmological
Principle. Oxford University Press, New York.
von Neumann, J. (1955) Mathematical Foundations of Quantum Mechanics.
Princeton University Press, Princeton, N.J.
Warren, J. M., and Akert, K. (eds.) (1964) The Frontal Granular Cortex and
Behavior. McGraw-Hill, New York.
Weisstein, N., and Haber, R. N. (1965) A U-shaped backward masking function
in vision. Psychonomic Science, 2: 75-76.
Wheeler, J. A., and Zurek, W. H. (1983) Quantum Theory and Measurement.
Princeton University Press, Princeton, N.J.
Wigner, E. (1961) Remarks on the mind-body question. In: The Scientist
Speculates: An Anthology of Partly-baked Ideas, I. J. Good, ed., Heinemann,
London.
