Recent progress in reading the mind/mind control/brain scanning

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Dec 5, 2008, 7:41:01 AM12/5/08

Thought the articles below may also help illuminate some facts for
those many non-consensual human guinea-pigs/victims who have been
covertly experimented on to advance neuro-scientists--and other related
researchers--interests. I openly consider myself one and have placed
accounts of what it feels like available on the internet.

Just how unaware of the darker/more evil side of this whole mind-probing
terrain some leading neuro-scientists are, is apparent in G.
Miesenbock's article which I've pasted below. I've excerpted this
section and placed it before his complete article.

Best, Imelda, Cork/

Imelda O'Connor, Carrigaline, Co. Cork

Thursday, December 4, 2008

Scientists learn how to read our minds

'The award helps highlight the work of women in science,' says Eleanor
MaguireDICK AHLSTROM
Research into brain imaging helped an Irish woman based at University
College London to win the Royal Society's €37,500 Franklin Prize
THE FANCIFUL notion of mind-reading has moved from science fiction to
science fact. A research group in London led by an Irish scientist has
used brain scans and a computer to decipher a person's thoughts.
The work forms part of a major effort to understand how human memory
works, where it happens in the brain and whether knowing such things
might lead to better treatments for Alzheimer's and brain-damaged patients.
Research efforts by Prof Eleanor Maguire at University College London
last week earned her the Royal Society Rosalind Franklin Award. The
distinction, which includes a medal and a cash award of €37,500, also
requires the winner to give a public lecture on their work.
"I was delighted, it is quite a prestigious prize and I wasn't expecting
it," says Maguire. "It helps highlight the work done by women in science."
Maguire's work on human memory has proved startlingly successful.
Leading a team of six, she and colleagues have developed a mathematical
algorithm that can be used to read people's thoughts.
The work depends on conducting MRI-based functional brain scans where
the scanning equipment is able to see which parts of the brain "light
up" in response to a stimulus, Maguire explains. This is an indication
that work - a thought or a memory - is happening at that place at that
moment.
"I am trying to understand how the human brain allows us to form
memories, store memories and recollect memories," she says. "It is a
complicated question."
Groups all around the world are pursuing this research and the focus is
on a small body within the brain, the hippocampus. It measures no more
than about 4cm by 1cm, but has proven to be essential to memory, she
says. "It is really central to forming new memories and recollecting the
past."
Recent discoveries using MRI scans have shown that the hippocampus and
associated nearby structures allow memories to be formed, but these
areas are also fundamental to our ability to navigate through space, to
speculation on future events and also to imagination.
It was noteworthy that the same parts of the brain were responsible for
looking backward but also forward in space and in time, she believes.
"There is this whole core area in the brain responsible for these
critical functions. Our challenge is to see how the brain deals with
these basic functions and how these brain areas connect with each other."
Very sophisticated MRI scanning and computers are helping to explain
this complex process. The scans can read brain activity down to a space
about 1.5mm cubed, but they are now looking for a resolution down to
below 1mm.
Her team conducts a range of tests, for example asking the subject to
think about specific things or to recall a memory, and this is where the
mind-reading comes into play. "We are sort of getting involved in
mind-reading to understand what a person was thinking," she says.
They are also using virtual reality systems that allow a person to
imagine navigating through London while their brains undergo functional
scans.
Patterns of thought begin to emerge and these are analysed by computer
programmes known as "classifiers". These rely on self-learning and
improve as they analyse more brain scans, Maguire says.
In one test the virtual reality system takes the subject through
specific parts of London, and the classifier studies the individual's
brain response. "The classifier was able to tell where the person was
during the test just by reading out the brain responses," Maguire says.
The system was up to 90 per cent accurate in reading where a person was
in the virtual reality London at any given time just by analysing their
thoughts.
They are also finding that the classifiers are able to see similarities
in these thought patterns between subjects, which suggests that there is
a common response to a given stimuli. Very specific parts of the brain
respond, but the pattern of response is the same across subjects. "It is
a very exciting time in the field of memory at the moment."
Maguire received her BSc from University College Dublin, did a Master's
in Britain before completing a PhD while at Beaumont Hospital in Dublin.
Rosalind Franklin was an accomplished scientist whose crystallography
images of DNA were central to helping James Watson and Francis Crick
discover the double helix structure of DNA.
This article appears in the print edition of the Irish Times

_____________________________________________________

Excerpted from article Neural Light Show . . . by Gero Miesenbock.
Transcription of entire article following excerpt

An Unexpected Forerunner
Three days before the paper reporting these experiments was scheduled
for publication in the journal Cell, I was flying to Los Angeles to
deliver a lecture. A friend had given me Tom Wolfe’s recently published
coming-of-age novel I Am Charlotte Simmons, thinking I would enjoy its
depiction of neuroscientists, not to mention the material that had
earned the book the Literary Review’s Bad Sex in Fiction Award. On the
plane I came across a passage in which Charlotte attends a lecture on
the work of one José Delgado, who also remotely controls animal
behavior—not with light-driven, genetically encoded actuators but with
radio signals transmitted to electrodes he has implanted in the brain. A
Spaniard, Delgado risked his life to demonstrate the power of his
approach by stopping an angry bull in midcharge. This, Wolfe’s fictional
lecturer declares, is a turning point in neuroscience—a decisive defeat
of dualism, the notion that the mind exists as an
entity separate from the brain. If Delgado’s physical manipulations of
the brain could change an animal’s mind, so the argument went, the two
must be one and the same.

I almost fell out of my seat. Was Delgado a fictional character, or was
he real? Immediately after landing in L.A., I did a Web search and was
directed to a photograph of the matador with the remote and his bull.
Delgado, I learned, had been a professor at my very own institution,
Yale, and had written a book entitled Physical Control of the Mind:
Toward a Psychocivilized Society, which appeared in 1969. In it, he
summarized his efforts to control movements, evoke memories and
illusions, and elicit pleasure or pain [see “The Forgotten Era of Brain
Chips,” by John Horgan; Scientific American, October 2005]. The book
concludes with a discussion of what the ability to control brain
function might imply for medicine, ethics, society and even warfare.
Against this background, I should probably not have been surprised when
the phone rang the day our paper was published and a U.S.-based
journalist asked, “So, when are we going to invade another country
with an army of remote-controlled flies?”

The media attention did not stop there. The next day the headline of the
Drudge Report screamed, “Scientists Create Remote-Controlled Flies,”
topping news of Michael Jackson’s latest court appearance. I assume it
was this source that inspired a sketch on the Tonight Show a week or so
later, in which host Jay Leno piloted a remote-controlled fly into
President George W. Bush’s mouth—the first practical application of our
new technology.

___________________________________________________________

Scientific American Magazine - September 24, 2008
Neural Light Show: Scientists Use Genetics to Map and Control Brain
Functions
A clever combination of optics and genetics is allowing neuroscientists
to identify and control brain circuits with unprecedented precision

Gero Miesenbock

In 1937 the great neuroscientist Sir Charles Scott Sherrington of the
University of Oxford laid out what would become a classic description of
the brain at work. He imagined points of light signaling the activity of
nerve cells and their connections. During deep sleep, he proposed, only
a few remote parts of the brain would twinkle, giving the organ the
appearance of a starry night sky. But at awakening, “it is as if the
Milky Way entered upon some cosmic dance,” Sherrington reflected.
“Swiftly the head-mass becomes an enchanted loom where millions of
flashing shuttles weave a dissolving pattern, always a meaningful
pattern though never an abiding one; a shifting harmony of subpatterns.”

Although Sherrington probably did not realize it at the time, his poetic
metaphor contained an important scientific idea: that of the brain
revealing its inner workings optically. Understanding how neurons work
together to generate thoughts and behavior remains one of the most
difficult open problems in all of biology, largely because scientists
generally cannot see whole neural circuits in action. The standard
approach of probing one or two neurons with electrodes reveals only tiny
fragments of a much bigger puzzle, with too many pieces missing to guess
the full picture. But if one could watch neurons communicate, one might
be able to deduce how brain circuits are laid out and how they function.
This alluring notion has inspired neuroscientists to attempt to realize
Sherrington’s vision.

Their efforts have given rise to a nascent field called optogenetics,
which combines genetic engineering with optics to study specific cell
types. Already investigators have succeeded in visualizing the functions
of various groups of neurons. Furthermore, the approach has enabled them
to actually control the neurons remotely—simply by toggling a light
switch. These achievements raise the prospect that optogenetics might
one day lay open the brain’s circuitry to neuroscientists and perhaps
even help physicians to treat certain medical disorders.

Enchanting the Loom
Attempts to turn Sherrington’s vision into reality began in earnest in
the 1970s. Like digital computers, nervous systems run on electricity;
neurons encode information in electrical signals, or action potentials.
These impulses, which typically involve voltages less than a tenth of
those of a single AA battery, induce a nerve cell to release
neurotransmitter molecules that then activate or inhibit connected cells
in a circuit. In an effort to make these electrical signals visible,
Lawrence B. Cohen of Yale University tested a large number of
fluorescent dyes for their ability to respond to voltage changes with
changes in color or intensity. He found that some dyes indeed had
voltage-sensitive optical properties. By staining neurons with these
dyes, Cohen could observe their activity under a microscope.

Dyes can also reveal neural firing by reacting not to voltage changes
but to the flow of specific charged atoms, or ions. When a neuron
generates an action potential, membrane channels open and admit calcium
ions into the cell. This calcium influx stimulates the release of
neurotransmitters. In 1980 Roger Y. Tsien, now at the University of
California, San Diego, began to synthesize dyes that could indicate
shifts in calcium concentration by changing how brightly they
fluoresced. These optical reporters have proved extraordinarily
valuable, opening new windows on information processing in single
neurons and small networks.

Synthetic dyes suffer from a serious drawback, however. Neural tissue is
composed of many different cell types. Estimates suggest that the brain
of a mouse, for example, houses many hundreds of types of neurons plus
numerous kinds of support cells. Because interactions between specific
types of neurons form the basis of neural information processing,
someone who wants to understand how a particular circuit works must be
able to identify and monitor the individual players and pinpoint when
they turn on (fire an action potential) and off. But because synthetic
dyes stain all cell types indiscriminately, it is generally impossible
to trace the optical signals back to specific types of cells.

Genes and Photons
Optogenetics emerged from the realization that genetic manipulation
might be the key to solving this problem of indiscriminate staining. An
individual’s cells all contain the same genes, but what makes two cells
different from each other is that different mixes of genes get turned on
or off in them. Neurons that release the neurotransmitter dopamine when
they fire, for instance, need the enzymatic machinery for making and
packaging dopamine. The genes encoding the protein components of this
machinery are thus switched on in dopamine-producing (dopaminergic)
neurons but stay off in other, nondopaminergic neurons.

In theory, if a biological switch that turned a dopamine-making gene on
was linked to a gene encoding a dye and if the switch-and-dye unit were
engineered into the cells of an animal, the animal would make the dye
only in dopaminergic cells. If researchers could peer into the brains of
these creatures (as is indeed possible), they could see dopaminergic
cells functioning in virtual isolation from other cell types.
Furthermore, they could observe these cells in the intact, living brain.
Synthetic dyes cannot perform this type of magic, because their
production is not controlled by genetic switches that flip to on
exclusively in certain kinds of cells. The trick works only when a dye
is encoded by a gene—that is, when the dye is a protein.

The first demonstrations that genetically encoded dyes could report on
neural activity came a decade ago, from teams led independently by
Tsien, Ehud Y. Isacoff of the University of California, Berkeley, and
me, with James E. Rothman, now at Yale University. In all cases, the
gene for the dye was borrowed from a luminescent marine organism,
typically a jellyfish that makes the so-called green fluorescent
protein. We tweaked the gene so that its protein product could detect
and reveal the changes in voltage or calcium that underlie signaling
within a cell, as well as the release of neurotransmitters that enable
signaling between cells.

Armed with these genetically encoded activity sensors, we and others
bred animals in which the genes encoding the sensors would turn on only
in precisely defined sets of neurons. Many favorite organisms of
geneticists—including worms, zebra fish and mice—have now been analyzed
in this way, but fruit flies have proved particularly willing to spill
their secrets under the combined assault of optics and genetics. Their
brains are compact and visible through a microscope, so entire circuits
can be seen in a single field of view. Furthermore, flies are easily
modified genetically, and a century of research has identified many of
the genetic on-off switches necessary for targeting specific groups of
neurons. Indeed, it was in flies that Minna Ng, Robert D. Roorda and I,
all of us then at Memorial Sloan-Kettering Cancer Center in New York
City, recorded the first images of information flow between defined sets
of neurons in an intact brain. We have since
discovered new circuit layouts and new operating principles. For
example, last year we found neurons in the fly’s scent-processing
circuitry that appear to inject “background noise” into the system. We
speculate that the added buzz amplifies faint inputs, thus heightening
the animal’s sensitivity to smells—all the better for finding food.

The sensors provided us with a powerful tool for observing communication
among neurons. But back in the late 1990s we still had a problem. Most
experiments probing the function of the nervous system are rather
indirect. Investigators stimulate a response in the brain by exposing an
animal to an image, a tone or a scent, and they try to work out the
resulting signaling pathway by inserting electrodes at downstream sites
and measuring the electrical signals picked up at these positions.
Unfortunately, sensory inputs undergo extensive reformatting as they
travel. Consequently, knowing exactly which signals underlie responses
recorded at some distance from the eye, ear or nose becomes harder the
farther one moves from these organs. And, of course, for the many
circuits in the brain that are not devoted to sensory processing but
rather to movement, thought or emotion, the approach fails outright:
there is no direct way of activating these circuits with
sensory stimuli.

From Observation to Control
An ability to stimulate specific groups of neurons directly, independent
of external input to sensory organs, would alleviate this problem. We
wondered, therefore, if we could develop a package of tools that would
not only provide sensors to monitor the activity of nerve cells but
would also make it possible to readily activate only selected neuron types.

My first postdoctoral fellow, Boris V. Zemelman, now at the Howard
Hughes Medical Institute, and I took on this problem. We knew that if we
managed to program a genetically encoded, light-controlled actuator, or
trigger, into neurons, we could overcome several obstacles that had
impeded electrode-based studies of neural circuits. Because only a
limited number of electrodes can be implanted in a test subject
simultaneously, researchers can listen to or excite only a small number
of cells at any given time using this approach. In addition, electrodes
are difficult to aim at specific cell types. And they must stay put,
encumbering experiments in mobile animals.

If we could tap a genetic on-off switch to help us find all the relevant
neurons (those producing dopamine, for instance) and if we could use
light to control these cells in a hands-off manner, we would no longer
have to know in advance where in the brain these neurons were located to
study them. And it would not matter if their positions changed as an
animal moved about. If stimulation of cells containing the actuators
evoked a behavioral change, we would know that these cells were
operating in the circuit regulating that behavior. At the same time, if
we arranged for those same cells to carry a sensor gene, the active
cells would light up, revealing their location in the nervous system.
Presumably, by rerunning the experiment repeatedly on animals engineered
to each have a different cell type containing an actuator, we would
eventually be able to piece together the sequence of events leading from
neural excitation to behavior and to identify all the
players in the circuit. All we needed to do was discover a genetically
encodable actuator that could transduce a light flash into an electrical
impulse.

To find such an actuator, we reasoned that we should look in cells that
normally generate electrical signals in response to light, such as the
photoreceptors in our eyes. These cells contain light-absorbing
antennae, termed rhodopsins, that when illuminated instruct ion channels
in the cell membrane to open or close, thereby altering the flow of ions
and producing electrical signals. We decided to transplant the genes
encoding these rhodopsins (plus some auxiliary genes required for
rhodopsin function) into neurons grown in a petri dish. In this simple
setting we could then test whether shining light onto the dish would
cause the neurons to fire. Our experiment worked—in early 2002, four
years after the development of the first genetically encoded sensors
able to report neural activity, the first genetically encoded actuators
debuted.

Remote-Controlled Flies
More recently, investigators have enlisted other light-sensing proteins,
such as melanopsin, which is found in specialized retinal cells that
help to synchronize the circadian clock to the earth’s rotation, as
actuators. And the combined efforts of Georg Nagel of the Max Planck
Institute for Biophysics in Frankfurt, Karl Deisseroth of Stanford
University and Stefan Herlitze of Case Western Reserve University have
shown that another protein, called channelrhodopsin-2—which orients the
swimming movements of algae—is up to the job. There are also a variety
of genetically encoded actuators that can be controlled via
light-sensitive chemicals synthesized by us and by Isacoff and his U.C.
Berkeley colleagues Richard H. Kramer and Dirk Trauner.

The next step was to demonstrate that our actuator could work in a
living animal, a challenge I posed to my first graduate student, Susana
Q. Lima. To obtain this proof of principle, we focused on a particularly
simple circuit in flies, one consisting of just a handful of cells. This
circuit was known to control an unmistakable behavior: a dramatic escape
reflex by which the insect rapidly extends its legs to achieve liftoff
and, once airborne, spreads its wings and flies. The trigger initiating
this action sequence is an electrical impulse emitted by two of the
roughly 150,000 neurons in the fly’s brain. These so-called command
neurons activate a subordinate circuit called a pattern generator that
instructs the muscles moving the fly’s legs and wings.

We found a genetic switch that was always on in the two command neurons
but no others—and another switch that was on in neurons of the pattern
generator but not in the command neurons. Using these switches, we
engineered flies in which either the command neurons or the
pattern-generator neurons produced our light-driven actuator. To our
delight, both kinds of flies took off at the flash of a laser beam,
which was strong enough to penetrate the cuticle of the intact animals
and reach the nervous system. This confirmed that both the command and
pattern-generating cells participated in the escape reflex and proved
that the actuators worked as intended. Because only the relevant neurons
contained the genetically encoded actuator, they alone “knew” to respond
to the optical stimulus—we did not have to aim the laser at specific
target cells. It was as if we were broadcasting a radio message over a
city of 150,000 homes, only a handful of which
possessed the receiver required to decode the signal; the message
remained inaudible to the rest.

One nagging quandary remained, however. The command neurons initiating
the escape reflex are wired to inputs from the eyes. These inputs
activate the escape circuit during a “lights-off” transition, as happens
when a looming predator casts its shadow. (You know this from your
fly-swatting attempts: whenever you move your hand into position, the
animal annoyingly jumps up and flies away.) We worried that in our case,
too, the escape reflex might be a visual reaction to the laser pulse,
not the result of direct optical control of command or
pattern-generating circuits.

To eliminate this concern, we performed a brutally simple experiment: we
cut the heads off our flies. This left us with headless drones (which
can survive for a day or two) that harbored the intact
pattern-generating circuitry within their thoracic ganglia, which form
the rough equivalent of a vertebrate’s spinal cord. Activating this
circuit with light propelled the otherwise motionless bodies into the
air. Although the drones’ flights often began with tumbling instability
and ended in spectacular crashes or collisions, their very existence
proved that the laser controlled the pattern-generating circuit
itself—there was no other way these headless animals could detect and
react to light. (The drones’ clumsy maneuvers also illustrated vividly
that the Wright brothers’ great innovation was the invention of
controlled powered flight, not simply powered flight.)

We also engineered flies with light switches attached only to neurons
that make the neurotransmitter dopamine. When exposed to the laser’s
flash, these flies suddenly became more active, walking all around their
enclosures. Previous studies had indicated that dopamine helps animals
predict reward and punishment. Our fly findings are consistent with this
scenario: the animals not only became more active, they also explored
their environment differently, as if reacting to an altered expectation
of gain or loss.

An Unexpected Forerunner
Three days before the paper reporting these experiments was scheduled
for publication in the journal Cell, I was flying to Los Angeles to
deliver a lecture. A friend had given me Tom Wolfe’s recently published
coming-of-age novel I Am Charlotte Simmons, thinking I would enjoy its
depiction of neuroscientists, not to mention the material that had
earned the book the Literary Review’s Bad Sex in Fiction Award. On the
plane I came across a passage in which Charlotte attends a lecture on
the work of one José Delgado, who also remotely controls animal
behavior—not with light-driven, genetically encoded actuators but with
radio signals transmitted to electrodes he has implanted in the brain. A
Spaniard, Delgado risked his life to demonstrate the power of his
approach by stopping an angry bull in midcharge. This, Wolfe’s fictional
lecturer declares, is a turning point in neuroscience—a decisive defeat
of dualism, the notion that the mind exists as an
entity separate from the brain. If Delgado’s physical manipulations of
the brain could change an animal’s mind, so the argument went, the two
must be one and the same.

Since then, researchers have used the light-switch approach to control
other behaviors. Last October, Deisseroth and his Stanford colleague
Luis de Lecea announced the results of a mouse study in which they used
an optical fiber to deliver light directly to neurons that produce
hypocretin—a neurotransmitter in the form of a small protein, or
peptide—to see whether these neurons regulate sleep. Researchers had
suspected that hypocretin plays this role because certain breeds of dogs
lacking hypocretin receptors suffer sudden bouts of sleepiness. The new
work revealed that stimulating hypocretin neurons during sleep tended to
awaken the mice, bolstering that hypothesis.

And in my lab at Yale, postdoctoral fellow J. Dylan Clyne used
genetically encoded actuators to gain insights into behavioral
differences between the sexes. The males of many animal species go to
considerable lengths in wooing the opposite sex. In the case of fruit
flies, males vibrate one wing to produce a “song” that females find
quite irresistible. To probe the neural underpinnings of this strictly
male behavior, Clyne used light to activate the pattern generator
responsible for the song. He found that females, too, possess the
song-making circuitry. But under normal circumstances they lack the
neural signals required for turning it on. This discovery suggests that
male and female brains are wired largely the same way and that
differences in sexual behaviors arise from the action of strategically
placed master switches that set circuits to either male or female mode.

Light Therapy
Thus far investigators have typically engineered animals to carry either
a sensor or an actuator in neurons of interest. But it is possible to
outfit them with both. And down the road, the hope is that we will be
able to breed subjects that have multiple sensors or actuators, which
would allow us to study assorted populations of neurons simultaneously
in the same individual.

Our newfound authority over neural circuits is creating enormous
opportunities for basic research. But are there practical benefits?
Perhaps, although I feel they are sometimes overhyped. Delgado himself
identified several areas in which direct control of neural function
could lead to clinical benefits: sensory prosthetics, therapy for
movement disorders (as has now become reality with deep-brain
stimulation for Parkinson’s disease), and regulation of mood and
behavior. He saw these potential uses as a direct and rational extension
of existing medical practice, not as an alarming foray into the ethical
quicksands of “mind control.” Indeed, it would seem arbitrary and
hypocritical to draw a sharp boundary between physical means for
influencing brain function and chemical manipulations, be they
psychoactive pharmaceuticals or the cocktail that helps you unwind after
a hard day. In fact, physical interventions can arguably be targeted and
dosed more
precisely than drugs, thus reducing side effects.

Some studies have already begun to probe the applicability of
optogenetics to medical problems. In 2006 researchers used
light-activated ion channels to restore photosensitivity to surviving
retinal neurons in mice with photoreceptor degeneration. They used a
virus to deliver the gene encoding channelrhodopsin-2 to the cells,
injecting it directly into the animals’ eyes. The patched-up retinas
sent light-evoked signals to the brain, but whether the procedure
actually brought back vision remains unknown.

Despite their theoretical appeal, optogenetic therapies face an
important practical obstacle in humans: they require the introduction of
a foreign gene—the one encoding the light-controlled actuator—into the
brain. So far gene therapy technology is not up to the challenge, and
the Food and Drug Administration is sufficiently concerned about the
associated risks that it has banned such interventions for the time
being, except for tightly restricted experimental purposes.

The immediate opportunity afforded by our control over brain circuits—or
even other electrically excitable cells, such as those that produce
hormones and those that make up muscle—lies in revealing new targets for
drugs: if experimental manipulations of cell groups X, Y and Z cause an
animal to eat, sleep or throw caution to the wind, then X, Y and Z are
potential targets for medicines against obesity, insomnia and anxiety,
respectively. Finding compounds that regulate neurons X, Y and Z may
well lead to new or better treatments for disorders that have no
therapies at the moment or to new uses for existing drugs. Much remains
to be discovered, but the future of optogenetics shines brightly.