1. health and fitness
2. disease

WINTER 2015
Artificial Intelligence | Henry Molaison | Tumor Paint | Memory Distortion | Selective Visual Attention
FEATURING
PROSOPAGNOSIA
Facial recognition
gone awry
THE LANGUAGE OF MUSIC
The Neuroscience of
Jazz improvisation
MYSTERIOUS MICROGLIA
Neurons are not the
only brain cells
www.greymattersjournal.com

Table of Contents
TABLE OF CONTENTS
BRAIN BLURBS
Artificial Intelligence:
8
In Memory of Henry Molaison
9
Optical Illusion
10
Tumor Paint
11
Tumor Paint Clinical Trials
12
Sleep and CSF
13
Amusia
14
Building Palaces of Memories
15
Early Childhood Neglect
16
FEATURED ARTICLE
IMAGINATION: A CONTAINER FOR INFINITY
17
By Lars Crawford | Illustrated by Tracy Montes
Imagining a vivid scene - with its sights, sounds, textures, and smells - is
something most people do with little to no trouble at all. But what enables such
behavior? How are the intricate, structures and complex computations going on
in your brain utilized to carry out these different forms of imagination?
RESEARCH ARTICLES
5
PROSOPAGNOSIA
THE LANGUAGE OF MUSIC
By Alec Sullivan
By Cody Kommers
Illustrated by Ellen Van Wyk
Illustrated by Nathan Jones
You identify your mother from your neighbor and your friend
from a stranger simply by their appearance. But imagine if
every face was a fresh face.
Bebop musicians created spontaneous music played at the
fastest speeds allowed by a music instrument. One has to
ask: how can the human brain produce jazz improvisation?
22
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GREY MATTERS | vol 2 | issue 1
25
29
31
MYSTERIOUS MICROGLIA
MEMORY DISTORTION
SELECTIVE VISUAL ATTENTION
By Brooks Gribble
By Eva Alderman
By Darren Hou
Illustrated by Justin Waterhouse.
Designed by Benjamin Cordy.
GREY MATTERS | vol 2 | issue 1
2

Editor’s Note
THE STAFF
ISSUE NOTES
BENJAMIN CORDY
JESSE MILES
LAUREN SELBY
Editor in Chief
Senior Editor
Editing Coordinator
Benjamin is a Neurobiology and Computational Neuroscience student pursuing
a career as a physician-researcher. He
gets overly excited by science history and
“discovery” stories. In his free time he enjoys reading, running, and rock climbing.
Jesse is a Neurobiology student investigating brainstem development. When he
grows up, he wants to be a science journalist and conduct research. Someone once
asked Jesse what he liked to do in his free
time - he could not answer.
Lauren studies Psychology
and English. Her interests
include neurobiology and
psychopathology, neuroscience and the law, and
good scientific writing.
ALICE BOSMA-MOODY
SNEHA INGLE
TYLER DEFRIECE
JUSTEN WATERHOUSE
Editing Coordinator
Events & Membership
Marketing Coordinator
Art Director - Graduated
Alice studies Neurobiology
and Bioengineering. She
plans to pursue a clinical
research career involving
neuro-prosthetics and rehabilitation.
Sneha is a Biology and Psychology student pursuing a
medical career focused on
the brain. She is the chief
architect behind An Evening with Neuroscience.
Tyler is a Neurobiology
student pursuing a medical
career involving the brain.
His is interested in mental
health, social neuroscience,
and consciousness.
Majoring in Painting and
Drawing and Philosophy,
Justen is interested in
using art to communicate
complex ideas of neuroscience to everyone.
STACIE SHIBANO
Layout Coordinator - Graduated
A recent graduate of the
Neurobiology
program,
Stacie pursues her interest
in art through Indesign.
She also enjoys hiking,
LOTR, and drinking tea.
3
AUTHORS
EDITORS
ARTISTS
Eva Alderman
Jasmine Correa
Lars Crawford
Alexa Erdogan
Brooks Gibble
Darren Hou
Jacob Gile
Cody Kommers
Oleg Kritsky
Nicole Riley
Alec Sullivan
Kirtana Vedire
Jacob Colter
Alexa Erdogan
Brooks Gibble
Chantruyen Ho
Oleg Kristsky
Maria Naushab
Katie Reil
Nicole Reno
Nicole Riley
Jennifer Wang
Nathan Jones
Chenhao Lu
Tracy Montes
Emma Rose
Sierra Schleufer
Ellen Van Wyk
Rachel Whitehead
GREY MATTERS | vol 2 | issue 1
EDITOR’S NOTE
ON THE COVER
Design by Benjamin Cordy
Art by Justin Waterhouse.
Imagining a vivid scene - with its sights,
sounds, textures, and smells - is something
most people do with little to no trouble at all.
But what enables such behavior?
HAVE YOUR SAY
If you have questions or comments regarding
this issue, please write a letter to the editor.
[email protected]
ONLINE
Visit the Grey Matters Blog for regular
neuroscience updates, stories, and articles.
greymattersjournal.com/blog
WRITE FOR GREY MATTERS
If you are interested in writing an article
for publication (print or blog), submit a
proposal online.
greymattersjournal.com/article-proposals
SPECIAL THANKS
Grey Matters Journal is funded, in part, by
the generous support of the departments of
Pharmacology, Psychology, Physiology &
Biophysics, the Neurobiology major, and the
College of Arts & Sciences at the University of
Washington.
We are especially grateful to those mentors
and advisors whose encouragement and
support make this publication a reality:
•
•
•
•
•
•
•
Dr. Ric Robinson,
Department of Biological Structure
Dr. William Moody
Department of Biology
Dr. Martha Bosma
Department of Biology
Dr. William Catterall
Department of Pharmacology
Dr. Stanley Froehner
Department of Physiology & Biophysics
Dr. Sheri Mizumori
Department of Psychology
Dr. Bruce Ransom
Department of Neurology
Last month I had the opportunity to discuss Grey Matters Journal with
a group of mentors and advisors who were interested in learning more
about the organization and its future. During the conversation I was
asked my favorite “why” question: Why does Grey Matters exist?
Scientists – in every field – are making great strides in revealing
the unknown. In recent months researchers have introduced synthetic
DNA into a living organism, landed a spacecraft on a comet, and are even
making headway with optical tractor beams.
Despite these exciting discoveries, the divide between discovery
and public engagement is a large as ever. While our society is heavily
dependent on the scientific method, it is largely uninterested in it. This is
a serious problem. The future of human health, security, and productivity
depends on our understanding of the world around us. Grey Matters
will continue its work as long as there is a need for science outreach
and education.
For Grey Matters, the development of accomplished science
communicators – including artists, illustrators, and designers – is as
important as neuroscience outreach. Thus, as part of this work, I am
happy to announce a new project: the Grey Matters’ Store.
In the coming weeks we will be selling a variety of undergraduatedesigned products, including: prints, posters, t-shirts, stickers, buttons,
mugs, water bottles, and more. All the proceeds are used to support
Grey Matters’ mission, which includes supporting students. That is why
half of every sale will go directly to the artist. The other half will only
be used for neuroscience outreach activities. The Grey Matters’ Store is
online at: www.greymattersjournal.com/store
In this issue of Grey Matters we take a look at the complex and
creative. The featured article, “Imagination: A Container for Infinity” by
Lars Crawford, takes a look at the “theatre of the mind” exploring the
research of imagination. In “The Language of Music”, Cody Kommers
discusses the relationship between language and improvised music.
I hope you enjoy it.
Benjamin Cordy
GREY MATTERS | vol 2 | issue 1
4
Prosopagnosia
Prosopagnosia
PROSOPAGNOSIA
An inability to
recognize faces
Image by Ellen Van Wyk
FRESH FACES
The human face is the index of the
mind. We differentiate between individuals and recognize familiar faces
based on one’s distinctive facial structure. You identify your mother from
your neighbor and your friend from a
stranger simply by their appear­ance.
But imagine if every face was a fresh
face.
Prosopagnosia, fittingly labeled
“face blindness,” is a disorder of face
perception where the ability to recognize faces is impaired. While anyone
can have trouble recognizing faces
out of context, prosopagnosics cannot identify their friends, relatives,
or even parents. They often complain
that they have trouble following movies or television shows because they
cannot recognize characters. Some
report difficulties in judging age,
gender, emotional expressions, or the
direction of a person’s gaze1.
Unlike amnesiacs, who also do
not recognize familiar faces, prosopagnosics have intact memories.
The distinguishing factor of the dis-
5
GREY MATTERS | vol 2 | issue 1
order: impaired facial recognition systems in the brain. The fusiform gyrus,
located in the occipital and temporal
lobes beneath the thalamus and hippocampus, is associated with facial
recognition. There are varying levels
of fusiform gyrus impairment linked
to neurological peculiarities such as
prosopagnosia, autism, hallucinations,
and synesthesia.
FORMS OF PROSOPAGNOSIA
Prosopagnosia can be present from
birth (developmental prosopagnosia)
or acquired. These forms differ in etiology and therefore, they will be addressed separately.
Developmental prosopagnosia establishes itself during early childhood
and there is no cure. Studies suggest
that genetic factors are responsible for
this condition, but a single gene has not
yet been identified2.
In an investigation to study genetic
factors, almost 700 randomly selected
students were administered a survey
which identified seventeen as prosopagnosics. The family members of
fourteen of these students were tested
for facial-recognition deficiencies, and
in all fourteen families, at least one
affected family member was found2.
These same researchers found that the
disorder is regularly transmitted from
generation to generation and proposed
that the prosopagnosia trait was dominant and transmitted through a single
mutation of an autosomal (non-sexlinked) gene2.
Acquired prosopagnosia results
from brain damage. This form of prosopagnosia was first documented in
1844, although reports of acquired face
blindness date to antiquity. Acquired
prosopagnosia lacks the genetic factors
proposed to underlie the developmental condition. Most individuals sustain
a closed head injury or suffer from a
stroke, and a lesion is formed in the
core neural regions responsible for normal facial processing. Some of the most
informative research on prosopagnosia
has dealt with these core regions, as
discussed in the following section.
face.
be noted, however, that these findings
were most strongly noted in non-human primates5.
The current understanding of face
perception considers these structures
to be the core of what is called the ventral occipitotemporal cortex (VOTC).
However, these regions constitute the
beginning of a broader network of extended nodes responsible for different
aspects of face processing such as gaze,
emotions, expressions, and face selectivity6. As a group, individuals with
prosopagnosia have shown reduced
facial selectivity in these core neural regions7. Curiously, though, some of the
participants studied did show normal
face selectivity7.
NEURAL BASIS OF FACIAL PROCESSING
The neural basis of face processing has
received extensive research attention
in the last two decades. Functional
neuroimaging studies show several
cortical regions with stronger responses to faces than to control stimuli, such
as objects. The most notable areas that
respond include the fusiform gyrus,
inferior occipital gyrus, and superior
temporal sulcus3.
The fusiform gyrus is part of the
temporal and occipital lobes. Within
the fusiform gyrus is the region linked
to facial recognition, known as the fusiform face area (FFA). During functional magnetic resonance imaging (fMRI),
this area produces twice the response
to face stimuli than to control stimuli
like houses, hands, the backs of human
heads, and flowers4.
The inferior occipital gyrus (IOG),
although difficult to identify exactly,
is a portion of the occipital lobe. Less
investigation has been completed for
this region, but evidence shows that the
IOG responds more strongly to faces
than to objects in greater than half of
participants scanned4.
The superior temporal sulcus is a
depression in the folds of the temporal
lobe. The cells in this location allow for
detection of changeable aspects of faces, such as gaze or expression. It should
FACE SELECTIVITY AS A TOOL TO STUDY
PROSOPAGNOSIA
One way to measure face selectivity
is through event related potentials
(ERPs). ERPs are the electrical
responses measured in the brain that
results from a particular neural event or
stimulus. These events can be sensory,
cognitive, or motor8. In our case, the
event is presentation of a face or nonface object.
The ERPs labeled M170 and N170
show a larger response to faces than
non-faces. Some individuals with developmental prosopagnosia showed
normal face selectivity, as measured
by these ERPs, while others did not,
which has lead scientists to question
the correlation between impaired facial
recognition and the variation in particular neural responses9. So, although researchers believe these responses may
be useful to identify different groups
of facial recognition deficiencies, they
have proved insufficient for identifying
prosopagnosics, which has led to further investigation of the brain circuitry
involved in this disorder.
According to more recent research,
individuals with developmental prosopagnosia exhibit reduced white matter tracts connecting the core VOTC to
parts of the extended face network. This
means that impaired facial perception
“
You identify your mother
from your neighbor
and your friend from a
stranger simply by their
appearance. But imagine
if every face was a fresh
GREY MATTERS | vol 2 | issue 1
6
Crossword Puzzle
Artificial Intelligence
may arise from a failure to propagate
signals between the core and extended nodes, rather than a dysfunctional
core10.
Taken together, these findings indicate that the core VOTC, the link between the core and extended nodes, or
the extended nodes themselves could
be the root of the disorder. This could
explain the variation in results from
research with prosopagnosics.
TREATMENT OF ACQUIRED PROSOPAGNOSIA
There is no formal treatment for prosopagnosia. However, there is the opportunity for those with prosopagnosia
to participate in experimental studies.
Some research focuses on advancing
the understanding of the causes and
neurological bases of prosopagnosia,
whereas other investigators are examining the effectiveness of training
programs designed to improve face
recognition.
A handful of published cases have
demonstrated focused attempts to provide rehabilitation. These suggest that
the lesions in the core face-processing
areas are resistant to treatment. Compensatory strategies such as the use of
voice, body shape, and gait to recognize
people, currently serve as a the best
treatment efforts11.
CONTINUED RESEARCH
Further investigation into prosopagnosia and the neurological basis of
face perception is needed. Examining
cases of acquired and developmental
prosopagnosia indicates existence of
a complex neural network devoted to
our recognition of faces. Consideration
of novel methods that yield improvement in facial recognition is necessary
to aid those that currently suffer from
prosopagnosia. In studying the mechanism of a malfunctioning facial recognition system, a more holistic and neural-based face perception theory can
be shaped. Maybe once this has been
accomplished the idea of a familiar face
will be conceivable to everyone.
2. A seahorse shaped brain
region extremely important
for memory formation.
3. A type of synapse
characterized by a more
negative post-synaptic cell
membrane potential.
5. A general term for a
collection of neuronal cell
bodies in the peripheral
nervous system (PNS).
6. An excitatory
neurotransmitter that plays a
key role in synaptic plasticity.
7. This brain region links
the nervous system and the
endocrine system.
8. A brain region that
is generally involved in
processing emotional
reactions and stimuli.
13. A neurotransmitter that
is chiefly responsible for
regulating mood, sleep, and
appetite.
14. This sleep state accounts
for the majority of a typical
sleep bout (acronym).
By Alec Sullivan
References on page 33
ACROSS
1. The molecule responsible
for initiating the first step in
visual perception.
4. A neurological disorder
marked by an inability to
regulate sleep-wake cycles.
9. A monovalent ion that is
generally responsible for the
repolarization phase following
an action potential.
10. A neurotransmitter that is
typically inhibitory.
11. A noninvasive recording
technique that uses electrodes
placed on the scalp.
12. This bivalent ion is
critically involved in the
release of neurotransmitters
following a depolarization
event in the presynaptic
neuron.
15. A glial cell in the CNS that
provides structural support,
maintenance of the bloodbrain barrier, and synapse
pruning.
Crossword by Oleg Kritsky
See page XX for solutions
Solution on page 21
7
GREY MATTERS | vol 2 | issue 1
A LOOK AT NEURAL NETWORKS
The study of how computers can
make decisions autonomously.
Image by Justin Waterhouse
CROSSWORD PUZZLE
DOWN
ARTIFICIAL INTELLIGENCE:
learn to make decisions such as those
involved in pattern recognition.
By copying the structure and
gen­eral function of biological neural
networks, computers are becoming
capable of accomplishing tasks that
were previously considered impossible.
One famous example is driving a car.
Human drivers divide their attention
between the roadway, traffic signals
and speed limit signs, as well as other
Can artificial neural networks spur the next computing revolution?
drivers. They make important decisions in real time using what they can
The brain’s processing prowess has the network’s actual output and its see and hear, and mistakes can be
prompted many to wonder whether expected output to modify thresholds. costly.
computers could become “smarter” by This utilizes a trial-and-error mechaThe pattern-recognizing power promimicking human brains. This might nism analogous to human learning.
vided by neural networks has proven
be accomplished by designing artificial
So what does this accomplish? to be critically important for this task.
neural networks, a manufactured ana- Usually, machines are fast at number Taking advantage of this, computer
log of our biological circuits.
crunching but fall short in tasks such scientists from Mahidol University in
An artificial network is a set of as image recognition. When someone Thailand trained an artificial neural
connected nodes that takes input from, looks at a picture of a cat, the human network to accurately determine what
and produces output for, neighboring brain can almost immediately recog- type of traffic signs were within its
nodes1. Organized this way, the network nize it. For most computers, however, field of view3. The speed of artificial
acts as a neural circuit and individual tasks that involve deciding whether neural networks provides real-time
nodes behave as neurons. Indeed, the an object exists in an image are more information about the environment
node will only produce an output signal difficult. Such tasks are fraught with and minimizes the chance that a decionce the input from neighboring nodes potential complications: the cat could sion would result in an accident.
reaches a threshold value.
be blurry, or only its tail may be visible,
Artificial neural networks provide
This is analogous to how a bio- or perhaps it is a toy kitten.
a new way to teach machines to do
logical neuron produces an action
Learning general patterns to identify more work on our behalf. Who knows,
potential based on whether it received objects is complicated, but something the maybe Artificially Intelligent drivers
sufficient input from pre-synaptic neu- human brain does with ease. Artificial will soon chauffeur you around town. rons. An important consideration in Intelligence borrows from nature by
constructing artificial neural networks abstracting a mathematical model of
is how best to establish the threshold the neural networks in our brains2.
value. One approach called supervised These artificial neural networks are
By Jacob Gile
learning uses the difference between powerful tools that allow computers to
References on page 33
GREY MATTERS | vol 2 | issue 1
8
Henry Molaison
Optical Illusion
IN THE MEMORY OF
HENRY MOLAISON
“
FEBRUARY 26, 1926 – DECEMBER 2, 2008
“
Scientists have grappled with the question of how memories
are stored for quite some time. Today many technologies
exist that allow for a variety of approaches to answering this
question, but one tactic that has withstood the test of time
has been the study of amnesiacs1. Henry Molaison, referred
to as patient H.M., was one such amnesiac who gained fame
for his willingness to partake in scientific studies. Over 100
scientists and teams have studied H.M., making him one
of the most heavily examined amnesiacs of all time1. Over
the years, study of H.M.’s brain helped to reveal some of the
structural components of memory2.
H.M. was not always an amnesiac. In 1953 at the age of
27, H.M. elected to undergo an experimental surgery called a
bilateral medial temporal lobectomy to control his eplepsy3,4.
This surgery removed part of the hippocampus, amygdala,
and other pieces of the cortex nearby3,4. While this surgery
drastically reduced the number of seizures that H.M. experienced, it came at a cost – H.M. developed both anterograde
amnesia and partial retrograde amnesia2,3,4.
By creating functional deficits in H.M. that were so specific to memory while leaving other intellectual abilities (such
as personality and IQ) unaffected, the surgeon unknowingly
created a way to study the brain structures involved in memory1,2,3,4. The thought emerged that if H.M. could not perform
tasks that people without the lobectomy could, the brain
structures removed from H.M. were in some way related to
memory1,2,3.
Research teams have revealed that H.M. does not suffer
from deficits in working memory, classical conditioning, or
motor skill learning1,2,3. For example, H.M. was given the
task of tracing a star while only able to see his drawing hand
in a mirror2,3. H.M. improved in his performance over time
even though he had no recollection of ever completing the
task, indicating a lack of declarative memory, but presence
of some degree of procedural memory2,3.
9
RETROOGRADE AMNESIA
The inability to create new
memories after the event that
causes amnesia.
The inability to recall memories that occurred before the
event that caused amnesia.
H.M.’s brain following his death1. The purpose of this dissection was to clarify exactly which structures were removed in
the original lobectomy. Histological slices of the brain were
prepared under strict protocol and pictures of these stained
slices were taken1. These pictures, along with previous measurements of H.M.’s brain structures, allowed Annese’s team
to create a 3D model of H.M.’s brain1.
New insight garnered from this work revealed that less
of H.M.’s hippocampus was removed than was originally
assumed1. However, it was noted that a part of the hippocampus known as the entorhinal cortex was removed, and
What H.M. lost, we now know,
was a critical part of his identity.
—Dr. Thomas Carew
ANTEROGRADE AMNESIA
OPTICAL ILLUSION
since the entorhinal cortex controls how information flows
through the hippocampus, this may have prevented the
hippocampus from functioning normally1. Along with this,
removal of H.M.’s amygdala was confirmed, which may explain some of H.M.’s “emotional unresponsiveness observed
in other studies1”. The researchers also discovered a previously undocumented lesion from the surgery in his frontal
lobe, the significance of which is currently unknown1.
This 3D reconstruction will allow other scientists to
analyze H.M.’s brain and will give the most accurate understanding of what specific brain structures were removed
during his lobectomy in 1953. Despite H.M.’s death, his legacy will live on and expand for years to come as researchers
continue to study the man we will always remember.
By Nicole Riley
References on page 33
Believe it or not, but all the lines in this optical illusion are
straight - not bent. Optical illusions highlight an important
fact about your brain: it is not a perfect recording device.
Rather, your brain reconstructs sensory stimuli to generate
your perception of the world.
Image by Justin Waterhouse
Additionally, H.M. was able to keep information in short
term memory, but would forget it as soon as he redirected
his attention2,3. This research revealed that different forms of
memory are stored in different parts of the brain2,3. Because
H.M. had his medial temporal lobes removed and he suffered
from anterograde amnesia, researchers concluded that the
medial temporal lobes are important for memory consolidation, which is the process by which a short term memory is
able to be stably converted to a long term memory2,3.
The majority of information about H.M.’s lesions came
from sketches drawn by the surgeon5. MRI imaging in later studies further clarified these original sketches, and revealed that H.M.’s brain lesion was not as large as originally
thought6. However, MRI images could not capture everything6. In order to fully understand the lesions in H.M.’s
brain, a post-mortem dissection needed to occur1. Because
H.M. agreed to donate his brain to scientific research, this
dissection was possible after his passing in 20081.
A research team at the Brain Observatory of San Diego,
led by Jacopo Annese, completed a broadcasted dissection of
GREY MATTERS | vol 2 | issue 1
GREY MATTERS | vol 2 | issue 1
10
Tumor Paint
Testing Tumor Paint
Image by Rachel Whitehead
T U M O R PA I N T
Currently, tumor removal in the brain is a high stakes guessing game. MRIs are used to reveal the location of brain tumors but are unable to display their location during a live
surgery. What’s more, up to this point it has been nearly
impossible to visually differentiate healthy tissue from tumor cells while operating. Instead, surgeons monitor the responsiveness of brain tissue by electrically stimulating areas
of interest, which shows whether or not these regions are
critical. With some innovative thinking and a little help from
nature, researchers are making steady progress on solving
some of the main problems that have made removal of brain
tumors such a gamble.
What makes tumor removal so perilous in the brain?
Because of the difficulty in distinguishing malignant and
11
healthy tissue, complications often arise during surgery
and, as a result, one of two situations likely occurs: either
healthy brain tissue is removed, or, some of the cancerous
cells remain. Incomplete excision of cancerous cells is common, and more than 80% of malignant cancers reoccur at
the site of surgery5. When the entirety of the tumor is removed, patients are more often than not left with impairments as a result of the operation. Simply removing a few
grams of healthy tissue from the brain can impair memory,
vision, movement, and a host of other things. The ability to
accurately distinguish between healthy and cancerous tissue
could help improve patient prospects dramatically.
In order to alleviate some of the uncertainty associated
with tumor removal, Dr. Jim Olson from the Fred Hutchin-
GREY MATTERS | vol 2 | issue 1
son Cancer Research Center worked with teams
from Seattle Children’s Hospital and the University of Washington to develop a molecule that could
bind and identify tumor cells. The molecule, known
as Tumor Paint, is a compound made from a peptide
found in the venom of Israeli Deathstalker scorpions
known as Chlorotoxin, and a fluorescent molecule
called indocyanine green (ICG).
One may be skeptical about the notion of putting a component of scorpion toxin anywhere near
their brain, but Chlorotoxin is actually essentially
inert to mature nervous tissue6,8. The real benefit to
using Chlorotoxin resides in its ability to attach to
gliomas2,3, which are found at high concentrations
in tumor cells.
Tumor paint has been shown to be 500 times
more sensitive in cancerous cell detection than an
MRI and can be used not only for brain tumors, but
also for colon, prostate, skin, and breast cancers5.
Furthermore, Tumor Paint is revolutionary because
it allows surgeons to see the tumors during the physical surgery. The Chlorotoxin component consists of
36 amino acids, and specifically binds to isoform 2
of a matrix metalloproteinase (MMP2)2,7. There appears to be a correlation between the levels of MMP2
expressed and the likelihood of complete excision of
the tumor, likely due to the upregulation of MMP2
in cancers (most commonly glioblastomas), leading
to increased likelihood of Chlorotoxin binding3,7.
Along with this, MMP2 is not normally expressed in
the brain, so its presence there is another indicator
of cancerous tissue6.
When injected into the bloodstream of the patient, the Chlorotoxin peptide of Tumor Paint will
find and become internalized by cancer cells. During
surgery, these cells fluoresce when shown under a
near-infrared (NIR) imaging system. Charge coupled device (CCD) cameras allow surgeons to see
even low levels of fluorescent ICG attached to tumors1,4, making possible more accurate, less invasive surgeries.
Tumor paint offers a revolutionary approach to
the way we deal with brain tumors and other cancers. The ability to view a tumor during live surgery
would allow for more confident and accurate prognoses and excision. Clinical trials began enrollment
in December of 2013 in Australia and, if successful,
will continue their second round here in the United
States7.
Dr. Jim Olson. Image from Ted x Seattle.
Testing Tumor Paint:
Current Clinical Trials
In 2010, Dr. Jim Olson founded the Seattle-based company Blaze
Bioscience to test and develop Tumor Paint for clinical use. Tumor
Paint BLZ-100, Blaze Bioescience’s first candidate, is currently
undergoing clinical trials in Australia.
This first round of testing includes adult patients with
non-metastatic skin cancers to determine the safety and potential toxicity of intravenous injection of the compound. Phase 1 of
this trial, which is currently ongoing, is designed to determine
biologically safe levels of the compound. Phase 2 will test BLZ100 pharmacokinetics in the human body, as well as fluorescence
studies in resected cancerous tissue. Patients will be injected with
an initial dose of BLZ-100 before surgery, then placed into five
different treatment groups and administered varying levels of the
compound during the procedure. Clinicians will test for adverse
effects directly after injection, as well as several days following the
procedure1.
In September 2013 the United States Food and Drug Administration has approved Phase 1 Investigational New Drug clinical
trials in patients with grade I, II, III, and IV gliomas intended for
surgical removal2. This study is currently accepting candidates,
although Blaze Bioscience does not believe that BLZ-100 will be
available for commercial use until 20203.
Since the discovery of Tumor Paint, many have wondered if the tumor-binding properties of Chlorotoxin could
be combined with a tumor-killing agent to find and destroy any solid cancerous tumor in the body. Olson’s current research, and the future vision of Blaze Bioscience, is
to identify and isolate specific components of compounds
produced by plants and animals that will selectively bind
to cancerous cells. Project Violet, a crowd-funded initiative, hopes to identify, develop, and engineer optimized peptides, known as optides, for the detection and treatment of
malignant tissue4.
By Kirtana Vedire
By Alice Bosma-Moody
References on page 33
References on page 33
GREY MATTERS | vol 2 | issue 1
12
Sleep and CSF
Amusia
Image by Emma Rose
Evidence suggesting that sleep is crucial
to your health continues to pile up. A
recent finding published in Science has
shed light on one of the mechanisms
behind the restorative function of sleep.
It seems that while we sleep, our brain
is tidying up. During wakefulness, the
body produces many metabolic waste
products,
including
amyloid-beta
(Aβ) peptides, which are substantially
cleared from the brain during sleep.
The accumulation of Aβ in the interstitial space leads to the buildup of
plaques associated with Alzheimer’s
disease and dementia. These improperly functioning protein structures are
toxic to the cells that make up the central nervous system (CNS).
The exact mechanism by which
Aβ plaques lead to neurotoxicity is
not well understood. One hypothesis
is that Aβ may compete for insulin
receptors, causing inadequate glucose
metabolism, which eventually leads to
13
neurodegeneration – a landmark feature of Alzheimer’s disease.
In addition, research has shown
that Aβ is detrimental to glutamatergic
synaptic transmission and intracellular calcium homeostasis. Collectively,
these adverse effects of Aβ presence in
the interstitial space lead to irreversible neuronal damage.
Because of their neurotoxic effects,
the CNS needs to process and remove
metabolic byproducts such as Aβ. The
CNS lacks a conventional lymphatic
system that would otherwise perform
this task. It is, however, bathed in
another solution: cerebrospinal fluid
(CSF). CSF allows the brain to float
without collapsing on itself, protects
it from mechanical stress, facilitates
proper blood flow to the brain, and acts
as a “dumpster” that collects metabolic
waste produced in the CNS.
Sleep is associated with a whopping 60% increase in the interstitial
GREY MATTERS | vol 2 | issue 1
HOW THE
BRAIN
TAKES
OUT THE
GARBAGE
WHILE
YOU
SLEEP
space volume, which provides for
a dramatic increase in exchange of
material between the CSF and interstitial fluid (ISF). At the onset of sleep,
the increased ISF volume allows for
improved clearance of Aβ by “dumping”
it into the CSF, where Aβ is eventually
passed to the general blood circulation
to be degraded by the liver.
Sleep has been shown to be an
important factor in restoring one’s
health. This study shows that, in addition to the many benefits conferred by
sleep, it is also important in regulating
clearance of waste products that are
linked to neurodegenerative diseases
such as Alzheimer’s and dementia – a
powerful reminder that our brains need
a time to have their garbage taken out.
By Oleg Kritsky
References on page 33
Image by Tracy Montes
AMUSIA
INTRODUCTION
used to examine the neural wave patterns of amusic indiIn 1878, Professor Grant Allen reported a man who was viduals. The amusic brain did not respond to pitches that
unable to perceive differences in pitch. The subject described differed by one semi-tone, whereas the brains of control
that attending concerts was similar to sitting in a room for subjects could easily detect the difference. In order to beta few hours while nothing happened. Allen later termed ter map the amusic brain, researchers used a neuroimaging
his subject’s “auditory abnormality” as note-deafness and technique called voxel-based morphometry, which captures
his studies became the first record of congenital amusia in brain images and, using statistical mapping, localizes focal
medical literature. Amusia is now the common term used to brain points into voxels.
describe learning disabilities related to pitch differentiation,
Voxel-based mapping made it clear that amusic indimusic memory, and music recognition.
viduals had considerably less white matter in their inferior
frontal gyrus (IFG) compared to the control. Likewise, an
CONGENITAL AMUSIA
excess of grey matter was found in the IFG, a characterisTo assess the extent of amusia’s effects, in 2001 Dr. Isabelle tic shared by other neurological disorders, such as dyslexia.
Peretz performed several behavioral studies on 11 amusic This provided strong evidence for the involvement of the
individuals and 20 control subjects. The tests were com- inferior frontal gyrus in musical pitch encoding and melodic
prised of individual tones, familiar tunes, lyrics, dissonance, pitch memory. Still, further studies are necessary to verify
and speech. The results showed that amusia is not caused causation of congenital amusia by the relative levels of white
by complications in the auditory system, since the subjects and grey matter in this region of the brain.
could readily differentiate speech intonations. Additionally,
all the subjects were musically educated as children and CONCLUSION
adults, ruling out lack of musical exposure as a cause.
To many music lovers, this disorder might seem like a fate
Ultimately, amusia was found to be specific to fine-grained worse than death. Preferences aside, continued research
pitch perception, which is required to appreciate music but into congenital amusia may provide insight into the neural
not necessarily speech. This was demonstrated when amusic circuitry underlying our ability to understand and appreciindividuals could not report the difference between original ate music while simultaneously exposing the ways improper
classical pieces and dissonant versions where the pitch was wiring can cause musical learning disabilities.
shifted by a semitone. Subjects also had slight difficulties
recognizing familiar tunes based on temporal cues such as
rhythm. These behavioral studies provided a foundation for
determining the neurological basis of amusia.
By Jasmine Correa
In 2006, an event-related potential study (ERP) was
References on page 33
GREY MATTERS | vol 2 | issue 1
14
The Method of Loci
White Matter and Early Childhood Neglect
of loci6. After training, the participants showed an overall
improvement in information recall and increased activity in
brain regions associated with attention processes and visualization when compared to their recall performance without
the method of loci3. These findings suggest that the method
of loci demands greater attention and processing of visual
information from the brain, which may account for the increase in memory performance.
Though it seems that some people posses supernatural
memories, a closer look shows that the major difference between the information recall of an average individual and a
World Memory Champion is simply technique. Indeed, the
participants in these studies did not show higher than average intelligence, nor did they possess any unique neuro-
BUILDING PALACES OF MEMORIES
A GLIMPSE AT THE METHOD OF LOCI
In 6th century Thessaly, the poet Simonides of Ceos is leaving a nobleman’s banquet hall after a rather unfortunate
lyrical poem performance. As he steps outside, a loud crash
echoes behind him. He turns around to witness the roof of
the banquet hall caving in, crushing the guests under a pile
of rubble. The deceased are so badly disfigured that relatives
are unable to recognize their loved ones. It is then that Simonides speaks up, claiming he can identify the guests based on
where they were sitting. The poet has seemingly stumbled
onto a unique type of information recall: memory based on
visual arrangement7. Today, the same memory technique is
used by individuals like Gary Shang, who can memorize and
recite up to 65,536 digits of pi, and Dominic O’Brien, who
has won the World Memory Championships eight times.
Such impressive feats raise the question of what is so neurologically distinct about individuals who are able to utilize this
aptly named method of loci.
The method of loci is a memory technique that takes
advantage of the brain’s ability to manipulate spatial information. What distinguishes this method is its integration of
multiple memory techniques, such as visualization, association, and organization of information. Users of the method of
loci construct a mental map based on a familiar location, like
their apartment or neighborhood. By constructing personalized rooms within this mental location, the user can organize
information that is visually associated to other thoughts or
images. In a history room, for instance, one might find Napoleon Bonaparte handcuffed to actor Idris Elba as a reminder
of the name of the island where Bonaparte was first exiled.
As the user practices walking through these rooms and becoming more familiar with the “memory palace”, it presumably becomes easier to recall information quickly and in an
organized fashion1.
Over the years, a number of neuroscientists have attempted to explore the neurological underpinnings of the
method of loci. In the early 2000’s, a group of World Memory Champion participants took part in a study conducted by
neuroscientists from the UK. While testing the participants’
working memory, the researchers recorded changes in blood
flow in the brain using fMRI, assuming that increased blood
flow meant increased brain activity in that locus. The data
showed an increased amount of activity in specific brain regions linked to learning associations, spatial memory, and
navigation2. These findings support the participants’ claims
of utilizing the method of loci due to the technique’s dependence on spatial memory and mental navigation.
In a similar neuroimaging study, researchers examined
an individual who could recite the first digits of pi to over
15
Image by Chenhao Lu
65,000 decimal places3. An fMRI test was performed while
the participant recited the first 560 digits of pi. The resulting
data showed increased brain activity in regions involved in
high-level executive functions and decision-related processes4, along with working memory, cognitive flexibility, and
planning5. The researchers then gave the participant a string
of 100 random digits to remember and ran another fMRI test
while the participant worked on remembering the numbers.
The long-term memory encoding process of the random
string of numbers appeared on fMRI data as increased activity of motor and visual association areas. Both neuroimaging
studies thus suggest that spatial processing and visual processing/association are integral characteristics of the method of loci memory technique.
It is important to note, however, that these specific neuroimaging studies were conducted on individuals who were
already known to possess great memory capabilities. There
remains the question of whether ‘average’ individuals could
achieve similar memory enhancement using the method of
loci technique. In 2005, a group of Japanese researchers investigated a group of ‘average’ individuals who underwent
an fMRI scan before and after they were taught the method
GREY MATTERS | vol 2 | issue 1
WHITE
MATTER
AND EARLY
CHILDHOOD
NEGLECT
Image: White matter tracts rendered by the BioTensor application
developed at the University of Utah from Wikimedia Commons.
A study recently published in JAMA Pediatrics took a new
approach to studying the neurological effects of long-term
early childhood neglect. Unlike previous studies conducted
on this topic, Dr. Johanna Bick and colleagues were able to
perform a randomized clinical trial using young children in
Romania. The researchers created an experimental group
by randomly assigning children from six Romanian institutions, characterized by low caregiver-to-child ratios and a
lack of developmental experiences, to higher-quality foster
care through the Bucharest Early Intervention Project. In
addition, an age- and sex-matched group of children who
had never been separated from their biological parents acted
as a control in the study. Dr. Bick and colleagues were interested in the effects of these different experiences on the
anatomical structures. The method of loci therefore seems to
rely on an individual’s ability to integrate information from
areas of the brain involved in visualization, association, and
organization of information, which can be enhanced with
training. While the intricacies of this technique’s molecular
framework remain unknown, perhaps the method of loci can
act as a gateway to furthering our understanding of memory
and information recall.
By Alexa Erdogan
References on page 33
long-term development of white matter.
The study found that the early childhood neglect characteristic of Romanian institutions had statistically significant
impact on the normal development of white matter, particularly in the corpus callosum and areas of the brain responsible for limbic function and sensory processing. Additionally,
they found that children who had begun their lives in an
institution but who had been switched to a more nurturing
foster care environment showed white matter development
that more closely resembled that of the control group than
the institutional group. This led researchers to suggest that
remediation of early damage to white matter development
due to neglect could be possible, an exciting result for the
study.
It is important to note, however, that this study is only
a contribution to the research dedicated to studying the
impact of early childhood neglect. First, the findings regarding potential remediation of white matter development in
the foster group are limited by the fact that foster children
showed similar development of the corpus callosum compared to the institutional group, which suggests that if in fact
such remediation is possible, it may be incomplete. What’s
more, the inclusion of six different institutions, with no controls for the exact differences in conditions at each, could be
problematic in terms of consistency within the experimental
group. The study also fails to provide a detailed account of
the deficits children at such institutions might experience,
leaving questions about exactly how the three treatment
groups differ. However, despite these limitations, the study
offers a promising look at the effect of positive post-natal experiences on the development of the brain, even after neglect
in early childhood.
By Lauren Selby
References on page 33
GREY MATTERS | vol 2 | issue 1
16
Imagination: A Container for Infinity
Imagination: A Container for Infinity
I M A G I N AT I O N
A CONTAINER FOR INFINITY
Image by Tracy Montes
17
GREY MATTERS | vol 2 | issue 1
INTRODUCTION
Imagining a vivid scene - with its sights, sounds, textures,
and smells - is something most people do with little to no
trouble at all. But what enables such behavior? How are the
intricate structures and complex computations going on in
your brain utilized to carry out these different forms of imagination? Does motor imagination require the motor system?
Visual imagination the visual system? Auditory imagination
the auditory system? Of the many capabilities the brain is
endowed with, the ability to imagine is one that is as puzzling and complex as it is intriguing. This article will examine
some of the research that has been done to reveal how a mass
of cells bound by bone and blood can have the seemingly infinite capacity typical of human imagination.
THE ROLE OF MEMORY
When asking questions about how imagination works, one
must consider the role of memory. Episodic memory, the
ability to recollect autobiographical past experiences, is
thought to play a crucial role in the ability to imagine. For the
past several decades it has been widely viewed by memory
researchers that engaging episodic memory is a constructive
process rather than a reproductive one1. In other words, when
one remembers they are pulling together pieces of information from multiple sources and reconstructing the memory
for the conscious self instead of merely playing it back in full.
Support for this notion comes from memory errors, which
are thought to be reflective of the component-wise operations of this constructive process1.
Memory researchers Shacter and Addis have hypothesized that imperfection in recalling memory fragments is
actually conducive to imagination. Misconstruction of fragments allows the brain to piece together disparate bits of
previous experiences in novel ways as a means to imagine
and predict personalized future scenarios1. If this imaginative process, deemed episodic future thinking, occurs as
Shacter and Addis propose, then one should be able to see
neural correlates in similar areas to those where memory
processes occur.
To investigate this, researchers have conducted several
different neuroimaging studies where PET scans of subjects’
brains were taken to assess correspondences between imagined and remembered events. Participants were asked to
remember past events from their personal life and to imagine personal future events at two different temporal scales:
near (days/weeks) or distant (months/years)2,3,4. The studies
showed that the same areas light up for both memory and
imagination of such events. These areas include bilateral
frontopolar cortex, involved in self reference; medial temporal lobe (MTL) which contains the hippocampus, a structure
involved in memory formation; occipital cortex, involved in
visual perception; and areas that process other things, such
as semantics and emotional responses.
Interestingly, the variation in activation at different
event time scales correlate positively between memory and
imagination of events. More importantly though, a lesser
level of activation in these areas was observed when subjects
were asked to remember or imagine events not related to
themselves, such as one involving Bill Clinton.
These findings suggest two things: 1) that episodic future
thinking involves, to a greater extent, one’s personal event
timeline and 2) that more generalized imagination likely utilizes more/other areas than those mentioned above. Further
support for this comes from the fact that amnesic patients
(with damage to MTL) have difficulty both remembering and
imagining personal events but are more competent at remembering and imagining general events1. However, though
these neuroimaging studies hint at physiological mechanisms for some kinds of imagination, the daunting process
by which the imagination is actually perceived – that is seen,
heard, felt, and experienced within the brain – is largely a
mystery.
BRAIN COMPUTER INTERFACES AND MOTOR IMAGINATION
Though it is still unclear how the brain reacts to perceive different imagined events, it has been shown that certain kinds
of imaginative processes do utilize distinct brain regions.
Motor imagery, or the generation of an internal representation of a movement prior to and during its occurrence, is a
process that happens constantly within the motor system5.
Remarkably though, the execution of a movement is not
necessary for such imagery to occur. That is, the signal recorded within the motor cortex, the precentral gyrus, during
the imagination of a movement is identical spatially and
temporally and nearly so in magnitude to that of realized
movement6.
Several groups of scientists have begun to utilize this
phenomenon to create devices designed to aid those with
motor deficits. By recoding electrical activity associated with
intended movement in the motor cortex, researchers are
opening doors on both motor deficit treatments as well as
the mechanisms behind motor imagination.
For example, in 1995 Dr. Marc Jeannerod worked with
and trained a tetraplegic patient, known as T.S., to control a
robotic prosthetic hand via imagined movements in an effort to recover grasping function6. Over a period of several
months T.S. was trained to imagine moving several parts of
his body including his left and right hands and feet. Jeannerod used an electroencephalogram (EEG) based brain
computer interface (BCI) to record electrical activity that
occurred while T.S. imagined moving his limbs. At the conclusion of this training, the BCI was able to identify T.S.’s
motor intent and engage the prosthetic with 100% accuracy.
More recently in 2006, Hochberg et al. continued this
research by implanting a 96 microelectrode array in a tetraplegic patient known as M.N.7. Three years after M.N. suffered a spinal cord injury, Hochberg implanted the device in
his primary motor cortex where neuronal activity associated
GREY MATTERS | vol 2 | issue 1
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Imagination: A Container for Infinity
Imagination: A Container for Infinity
with imagined movements was still robust.
In this study, M.N. learned to modulate the
firing rates of a small group of neurons via
motor imagery in order to control different
devices, including a computer cursor and
several robotic arms. With one such robotic
arm, M.N. was able pick up and move an
object.
M.N.’s motor performance was not
affected by engaging in other cognitive
tasks such as conversing with Houchberg.
Perhaps superficially this is unsurprising as
M.N. is activating the same brain regions
as able-bodied individuals while simultaneously performing motor and cognitive
tasks. However, such simultaneous cognitive function in M.N. is actually quite
incredible. It suggests that M.N. may have
imagined the movement of the prosthetic
rather than the series of associated body
movements. In a sense, M.N. had recruited
Figure 1: Brain structures implicated for both memory and imagination of events.
the devices by imagination alone. Indeed,
Areas include the bilateral frontopolar cortex (red), medial temporal lobe (green), and
patients in other studies have reported
the occipital cortex (blue) among other structures.
such an experience. For example, patients
in a study by Miller et al., who utilized an
electrocorticography (ECoG) paradigm indicated that after sual cortical activity was disturbed via repetitive transcranial
only a few trials they merely had to imagine the movement of magnetic stimulation (rTMS).
a cursor in the desired direction rather than the motor comIn a similar vein, the act of imagining sound, related to
mand trained for and assigned to it8.
but not constrained by memory of sound, requires the audiMotor imagery is clearly a very powerful form of imag- tory system. An EEG study conducted by Brix demonstrated
ination as well as a simpler concept to grasp than other that both visual imagination potentials (VIP) and auditory
imaginative processes. Although the underlying conscious imagination potentials (AIP) occur over the visual and audecision process mediating this is still unknown, the physical ditory cortices, respectively, when subjects were asked to
output is far easier to understand and to design devices for imagine certain sights and sounds10. Also shown was that
compared to episodic future thinking and memory in gen- the amplitude of the evoked potential correlated with the
eral.
degree of concentration required by the subject to perform
the imagination. For example, a particularly intense auditory
VISUAL AND AUDITORY IMAGINATION
imagination, such as the sound of a song, produces a greater
Other imaginative processes related to memory are those of AIP than that of a simple one, such as the sound of a horn.
visual and auditory imagination. A suite of visual imagery Taken together, these studies show that when one engages in
paradigms have been carried out that indicate the visual sensory-motor imagery, they employ the associated modalsystem is involved in generating visual imaginations. One ity to do so.
study of particular intrigue by Kosslyn et al. observed activation within Broddman area 17, the primary visual cortex, MENTAL DISORDERS
via PET while subjects were asked to imagine and describe
Discussed so far are the imaginative processes in
a set of stripes, e.g. their width and orientation9. Intuitively, psychologically intact individuals where conscious effort
the activation was similar to that observed during actual vi- brought about the desired form of imagination. However,
sualization of a set of stripes. More notable though was the just as other cognitive functions can be impaired by neurosubjects’ inability to perform the imagery task while their vi- logical disorders, so too can one’s imagination.
REPETITIVE TRANSCRANIAL MAGNETIC STIMULATION (RTMS)
rTMS is a non-invasive technique to stimulate or inhibit neurons
using electromagnetic induction.
19
HALLUCINATIONS
perceiving something without stimulation of that sensory organ
GREY MATTERS | vol 2 | issue 1
Figure 2: Using BCIs, a quadraplegic woman directs a robotic arm to bring a chocolate bar to her mouth.
Several mental disorders bring about a sense of delusion that strips people of the ability to distinguish between
real and imaginary. Hallucinations are actually considerably
common but most individuals who observe them have the
cognitive faculty to know that what they are observing, be
it sight, sound, or other, is not real. For example, a disorder known as Charles Bonnet Syndrome (CBS) occurs in a
relatively large subpopulation of visually impaired individuals who report vivid hallucinations of random events that
are strictly visual11. Very few of the individuals estimated to
have CBS report their experiences for fear of being labeled as
mentally unstable, but most of those who do report indicate
they are fully aware the visions are not real.
Researchers have hypothesized that these hallucinations
occur when deafferentiating neurons in visual association
areas fire. It has been proposed that in such circumstances,
these dying cells, which do not typically fire, behave like they
would if they were responding to visual input. As a result,
the brain creates a narrative around the activity11. Though
bizarre, it is important to note that CBS individuals do not
interact with these hallucinations in any way.
The faculty that enables individuals to recognize that
imagined events are not real is known as reality-monitoring, and is thought to be a form of source memory, i.e. one’s
ability to remember the origin of information. When reality-monitoring malfunctions, serious psychological harm can
result. One particularly extreme example of such a loss in
reality-monitoring occurs within schizophrenics12. Schizophrenic patients have a range of symptoms including the
hallucination of voices and people. The difference between
individuals with disorders like CBS and those with Schizophrenia is that the latter often report expressly interacting
with their hallucinations, sometimes in frightful, harmful or
threating ways; their inability to reality-monitor results in
emotional responses to their hallucinations.
A study done by Brébion et al. demonstrated that schizophrenic patients have a reduced ability to reality-monitor
related to an increased propensity to report events that had
not explicitly occurred12. Patients were presented with a set
of pictures and words and then tested, after a brief delay,
for the form that each item took. Brébion et al. found that
patients with schizophrenia were twice as likely as controls
to misattribute the presentation of a word as an image. They
also observed that patients did poorly at recognizing which
items actually appeared as images in general. As such, Brébion et al. hypothesized that patients were engaging in excessive visual imagery which could have conflicted with internal
representation of target images. They also contended that
patients’ working memory, i.e. short term memory, could
have been involved due to the relative timing of the tasks.
It has been observed that both source memory and
working memory occur in the same area in the brain: the
prefrontal cortex13,14. Furthermore, several studies have
shown that cerebral blood flow to the prefrontal cortex is
reduced in schizophrenic patients14. Postmortem studies of
schizophrenic brains have shown a reduction in neuropil
(dendrites or axons of neurons) that has been thought to
result from this lack of blood flow to the prefrontal cortex,
GREY MATTERS | vol 2 | issue 1
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Imagination: A Container for Infinity
Mysterious Microglia
most notably in the supragranular layers, which are generally considered association areas of the brain15. Indeed,
an electrophysiological study in monkeys has shown that
there are ‘delay’ cells, within the supragranular layers of the
prefrontal cortex, thought to connect items of information
with one another13. Although the exact mechanisms behind
mental disorders like schizophrenia are vastly unknown, it is
clear that the brain sits delicately within its reality, and that
minor disturbances in function can turn imagination from a
beautiful and limitless tool into something frightening and
confusing.
FINAL THOUGHTS
Through the observation of the various studies reviewed
above, it is quite clear that imagination is a complex behavior that takes many forms via dispersed brain structures and
is extremely powerful. Creativity, the act of generating new
ideas or combining old ones in novel ways, is tightly related
to imagination and an attribute that humans are particularly
well-endowed with. Of course, like other human skills, imagination and creativity take time and practice, much of which
These are hippocampal neurons
growing in culture
The green marks a growth
protein called GAP43, and the
blue labels DNA
Processes at the ends of these
budding neural extensions are called
growth cones
Growth cones are enriched with a
huge diversity of receptors, which
guide growing neural extensions
to their final destination
begins when we are mere children. Countless psychological
studies have shown the benefits of imaginative play throughout development from early childhood and into adolescence
in producing creative and productive individuals16. The combinatorial process of ideas at work when children imagine
fantastic scenes and figures paves a path for not only creative
but also emotionally and socially adept lives in the future17.
With an activity as widespread in the brain and as
potent as imagination, one cannot help but think that the
human brain evolved so as to encourage the creation of a
boundless internal representation of the world for its own
manipulation. And, though it currently remains perplexing
how, as Charles Bonnet so eloquently put it, “the theater of
the mind is generated by the machinery of the brain,” such
understanding is not requisite to marvel at the limitless capability made possible by it.
By Lars Crawford
References on page 33
I
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t
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P o
n
o
t
h
G A B A
l
a
C a l c i u m
u
A s t
Image Credit: Encore Biotechnology Inc.
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l
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a
MYSTERIOUS
MICROGLIA
INTRODUCTION
In April 2013, President Barack Obama announced an initiative to fund approximately one hundred million dollars
of neuroscience research, called the Brain Research through
Advancing Innovative Neurotechnologies Initiative (BRAIN).
By encouraging and supporting the study of neurons, these
funds are hoped to shed more light on human brain function.
As wonderful as this is for neuroscience, BRAIN is forgetting
about a crucial class of cells in the brain – glial cells.
Have you ever heard of glia? Most people know little
about these brain cells, even though in some areas of the
brain they outnumber neurons two to one1.
Glial cells, or glia, are a family of non-neuronal brain
cells that, unlike neurons, do not generate action potentials
or have chemical synapses. Microglia are one of at least four
different types of glial cells, each of which have distinct roles
and abilities.
Microglia perform a variety of tasks that range from
supporting synapse development to promoting neuron
growth, and even apoptosis, or programmed cell death2. In
fact, research suggests that microglia dysfunction is related
to a slew of neurological disorders such as Alzheimer’s disease, Parkinson’s disease, depression, and schizophrenia3.
How do microglia do so much? And how does our
growing understanding contribute to the pathology of the
disorders mentioned above? Research on microglia has
increased dramatically in the last twenty years with the simple goal of understanding what role microglia have in normal
brain functioning.
HISTORY OF MICROGLIA
Scientists first discovered glial cells in the late 19th century, thanks to the groundbreaking work of Rudolf Virchow.
Microglia, however, weren’t specifically identified until the
early 20th century by neuroscientist Pio del Rio-Hortega.
Already there existed an understanding that the discovered glial cells were unlike typical neurons. Microglia were
GREY MATTERS | vol 2 | issue 1
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Mysterious Microglia
Photo by Frank Heppner
Mysterious Microglia
© Charité
the brain. It is estimated that microglia are able to scan nearly
the entire brain in just a few hours, searching for interlopers7.
When triggered by stimuli such as CNS injury or disease,
microglia rapidly undergo activation through complex pathways before changing structure to better face the stimulus6.
In addition, recent research indicates that microglia seem
to be involved in early brain development. Neuroscientists
have revealed evidence that microglia contribute to synaptic development and pruning in the brain’s early stages of
growth – an important role to say the least8.
So how do microglia accomplish such a variety of tasks?
It has been known for decades that microglia are capable
of altering their morphology, or shape, in order to change
their function, making them extremely diverse6. This ability
to switch between phenotypes has prompted scientists ask
what regulates these changes and what happens when the
mechanisms involved are disrupted.
Researchers discovered that there are actually two
main morphologies that microglia can express: ramified or
amoeboid.
Figure 1. Photo showing microglia (brown) clustering around
beta-amyloid plaques (red), indicators of Alzheimers’ Disease. An
example of research investigating the role of microglia in a mouse
model of Alzheimer’s disease.
RAMIFIED MICROGLIA
Ramified microglia, or “resting microglia,” are present in a
mature and healthy brain. This type of microglia was once
thought to simply rest in the CNS, awaiting activation;
however, publications are rapidly emerging, revealing that
not specifically involved in basic neuronal signaling; rather, ramified microglia are active participants not only in mainthey possessed an ability to change shape depending on their taining a healthy brain, but also in supporting a developing
environment4.
one.
Unfortunately, research on microglia seemed to go
Moving about the brain’s tissues, resting microglia do
on hiatus shortly after their discovery. Perhaps because not simply “rest.” They utilize chemotaxis to patrol for potenneurons were easier to study, it wasn’t until the late 20th tial targets such as pathogens or cells that have undergone
century when new techniques were developed that allowed apoptosis9. They have short, protruding processes that move
neuroscientists to answer specific questions about microglia around the cell body as the microglia move. These serve to
and their dynamic behavior.
increases the surface area of the microglial cell so that it can
be more efficient in scanning the CNS6.
CURRENT UNDERSTANDING
The ramified processes can be extended or retracted in
It is thought that microglia are akin to macrophages, one of mere minutes10. These extensions can even reach out and
the key cells in immune response and healing. Similar to make contact with other cells such as astrocytes, pre-synmacrophages, microglia are derived from bone marrow and aptic neurons, or post-synaptic neurons. This suggests that
are indeed involved in immune responses in the brain such microglia might posses the ability to regulate signal transas phagocytosis, or the engulfing of damaged cells and other mission, synapse development, and even plasticity – the
extracellular material5.
brain’s ability to change due to experience.
Microglia are the resident immune cells in the central
Ramified microglia can perform phagocytosis even in
nervous system (CNS). They defend the brain from any type the absence of their normal inflammatory stimuli8. It all
of inflammatory stimulus such as pathogens, blood loss, dis- depends on where in the brain these microglia are located. If,
ease, and more. They have the ability to move throughout for example, they are in the hippocampus, which is a structhe brain and help form the supporting structure of the CNS6. ture highly involved in memory formation and organization,
Microglia are also very sensitive to their environment and resting microglia might adopt this function to help prune
alter their physiology according to changes in brain chem- and rearrange synapses11.
istry and homeostasis. This will be further explored in later
The science behind microglia in the healthy adult brain
paragraphs.
is still relatively new; however, most studies hint at the idea
While they were once thought to be inactive for brief that microglia are not solely involved in responding to an
moments, microglia are never idle, as they constantly scan injured brain. New research has just started to address how
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GREY MATTERS | vol 2 | issue 1
microglial cell can phagocytize anything it needs to remove
from the surrounding brain tissue to help the brain return to
homeostasis14.
Microglia can also be “fully” or “over” activated, in
which they actually become neurotoxic to some extent. They
are then involved in a pro-inflammatory response, releasing nitric oxide, cytokines, and reactive oxygen species that
physically cause neuronal damage, or neurodegeneration15.
When properly regulated, this sort of response can be
beneficial to the brain. Constant or chronic activation of
microglia, however, can be potentially injurious to the surrounding brain cells, leading to neurodysfunction.
Essentially, activated microglia are effective in supporting and helping regenerate neurons, as well as removing
pathogens and inflammatory stimuli through phagocytosis
and the like. Microglia activation can also occur in a way that
is actually detrimental to brain health and function.
NEURODEGENERATIVE DISEASE
The complete mechanisms behind the activation pathways of microglia are not currently understood, but we do
Figure 2: Ramified “resting” microvglia are shown with their thin, know that an aging brain’s microglia tend to behave more
branched processes. Activated microglia, which can perform many abnormally. In younger brains, microglia seem to prefer
maintenance duties, are shown to have thicker, less extensive activation through the neuroprotective route, while in aging
projections. Amoeboid microglia, the most condensed and motile brains, microglia are more prone to over-activation and thus
microglia, are a type of activated microglia.
neurodegeneration16.
Questions remain regarding the changes in microglial
a given location in the brain influences ramified microglia response that could lead to neurodegeneration. Is it due to
behavior, as well as the extent to which these microglia con- microglial dysfunction? How much of a role does the aging
tribute to normal brain development.
brain play? When one considers the fact that Alzheimer and
Parkinson’s diseases are neurodegenerative and partially
AMOEBOID (“ACTIVATED”) MICROGLIA
brought upon by old age, it is fair to postulate that dysfuncMicroglial activation occurs when a ramified microglial cell tional microglia may contribute to the degeneration.
comes into contact with anything that disrupts homeostasis
This opens up a whole new range of possible therapies
within the brain. Once activated, the microglial cell under- for neurodegenerative diseases. Could microglia and regulagoes changes in gene expression and rapidly alters its shape tion of activation be an answer to mitigating symptoms such
to better attack the disrupting stimuli12.
as loss of brain cells or impaired brain function? This is one
Activated microglia adopt the amoeboid morphology – of many questions left to answer regarding microglia.
these cells are able to move around, usually towards their
target, and they retract their processes, becoming more CONCLUSION
spherical6. These blob-shaped microglia are still very envi- Microglia, the cells once thought to passively guard the brain,
ronment-specific; therefore, activated microglia can appear are now being shown to have expansive roles in the CNS.
and behave differently in one area of the brain ver­sus Although they are slightly less mysterious than they were
another.
even 20 years ago, microglia still remind us that we have
Each specific response, or activation state, also depends much left to learn about the brain. Only further questioning
on the stimuli, since amoeboid microglia function changes and research can uncover all that this dynamic cell can do.
depending on what it’s targeting. In certain cases, activated Until then, neuroscientists can only continue to unravel the
microglia can be stimulated to become alternatively acti- tantalizing mystery that is microglia.
vated, or neuroprotective13.
Alternatively, activated microglia can opt to release
neuronal growth factors that serve to aid damaged neurons
in regeneration. They can also prepare to engulf cellular debris or release molecules such as cytokines that are
By Brooks Gribble
involved in an anti-inflammatory response. In addition, the
References on page 33
GREY MATTERS | vol 2 | issue 1
24
The Language of Music
The Language of Music
BEBOP JAZZ
A new style of jazz began to emerge in New York City during
the mid-1940s, dubbed “bebop” by its pioneers. With its
trademark flurry of complicated melodic lines, bebop is the
musical equivalent of receiving every dish on the menu at
once. It dismantled the danceable swing style of the prior
era’s jazz; the music became fast, involved, and abstruse.
The epicenter of the bebop movement was Minton’s
Playhouse, a compact Harlem nightclub. Musicians did not
so much patronize Minton’s as rely on it for subsistence.
And among the favored musicians at Minton’s, performing
in the smoky den for a clientele equal parts eccentric and
drug-hazed, was Thelonious Monk. Any given evening at
Minton’s, Monk could be found at the piano, nurturing a
cigarette between his teeth.
Like that of any other bebop musician, Monk’s playing was characterized by a central facet: improvisation. In
contrast with current popular music heard on the radio or a
Mozart composition, the music played by bebop musicians
is made up on the spot—ex tempore. As if following a map
marked only with a start and an end, the musicians have an
idea of where they are and where they want to go, but they
have no set path for how to get there.
At the time, Monk and his contemporaries seemed
set to be painted onto the mural of modern music as
an inconsequential afterthought.
In contrast to the
popular acts of the era, bebop musicians had neither the polished image of Perry Como nor the endearing choruses of
Frank Sinatra. Bebop was not the kind of music one might
expect the typical post-war American to enjoy.
Yet, despite bebop’s gratuitous nonconformity, its innovators became icons of American artistry. Among many
other accolades, Monk won a Pulitzer Prize and a Grammy
Lifetime Achievement Award. Monk is the second most
recorded jazz composer of all time—an achievement that is
made more impressive when contrasted with how few songs
he actually composed. The most recorded jazz composer of
all time, Duke Ellington, penned over 1,000 songs; Monk
composed only 70.
Though Monk’s status as a figure of American music
may be curious, this story contains a more intriguing phenomenon: that Monk and his colleagues could play this
music in the first place. Bebop musicians created art characterized by its spontaneity while being produced at the fastest
speeds physically allowed by a musical instrument. Somehow improvisers used this manic, abstract music to create
meaningful works of art.
How can the human brain produce jazz improvisation?
Image by Nathan Jones
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GREY MATTERS | vol 2 | issue 1
NEURAL CORRELATES OF IMPROVISED MUSIC
Intrigued by this question, Johns Hopkins neurologists
Charles Limb and Allen Braun sought to find out which areas
of the brain activate in improvising musicians. Limb and
Braun recruited six professional jazz pianists — contempo-
rary Monks — for a functional magnetic resonance imaging
experiment. Limb and Braun faced the challenge of trying
to maximize scientific precision while recreating the authentic experience of a musician as closely as possible. Trading
the dimly lit stage at Minton’s for the sterile, white confines
of an MRI scanner required some ingenuity. To address
this issue, Limb and Braun designed a special keyboard
that would be safe in a powerful magnetic field while still
allowing the musicians to retain a realistic feeling of playing.
With this keyboard, the pianists played a sequence of songs,
some of which were memorized and some of which were
spontaneously composed. The only difference between the
two situations was whether or not the musicians improvised.
The variation between these brain states showed which areas
activated specifically for improvisation, beyond what was required simply to play piano1.
Limb and Braun’s first finding may have elicited an
I-could-have-told-you-that response from Monk. They
found deactivation in areas of the brain that are thought to
be concerned with what society will think about one’s actions. Two particular brain areas perk up when you know
the world is watching and choose to act according to societal
conventions; they are known as the dorsolateral prefrontal
cortex and the lateral orbitofrontal cortex. For Monk, who
frequently danced around on stage when tired of the piano,
deactivation of these areas was commonplace: “I say, play
your own way. Don’t play what the public wants.”
Limb and Braun’s second finding was more intriguing:
Jazz improvisation activates a region of the brain that Braun
and his colleagues had previously hypothesized is responsible for parsing narrative structure2. This area is known as
the medial prefrontal cortex. Further scrutiny is required to
substantiate their hypothesis, but preliminary evidence suggests that the medial prefrontal cortex contributes to how
one naturally tends to tell a story with a beginning, middle,
and end. This brain region is key to understanding how the
brain creates jazz improvisation.
NEUROLOGICAL SIMILARITIES BETWEEN
IMPROVISED MUSIC AND LANGUAGE
Monk played his solos much like he would tell a story. He
would present an initial musical idea; tinker with the details
of that idea, expanding on its key points; then present a conclusion—as if asking for your opinion. The narrative unfolds
fluently even though he is making this story up as he goes. A
drummer and bassist would have accompanied him, not as
passive audience members, but as confidants responding in
earnest to Monk’s ideas.
Compare this interaction among the members of
Monk’s band with a conversation you would have with a
friend, requiring attentive participation from you both. Your
conversation and Monk’s improvisation are remarkably similar. Both have basic narrative structure of exposition, development, and conclusion. Both relate complex information
GREY MATTERS | vol 2 | issue 1
26
The Language of Music
The Language of Music
without premeditation. Both require empathetic interaction
among participants.
This is not just a qualitative observation: Musical improvisation and spoken language are processed similarly in
the brain. The medial prefrontal cortex activation that Limb
and Braun saw in improvising musicians is the same region
would also likely be activated if you were telling a story to
a friend. It appears that the brain uses some of the same
regions to develop narrative structure in both improvised
music and conversation.
Charles Limb and a team of his students, led by Gabriel
Donnay, ran another jazz-inspired functional imaging study.
This time, they looked at improvisational interaction. Unsurprisingly, there is already an established paradigm in jazz
to facilitate conversation-like interaction called trading, in
which improvisers trade short musical phrases back and
forth in response to one another. Donnay and his team used
the same method of comparing improvisation with non-improvisation as before, but this time they scanned each subject while trading with another musician3.
Donnay and his team found a pattern of activation that
decidedly resembles what happens in the brain while participating in conversational language. Most notably, they saw
activation in an area concerned with structure of a different
kind, of sentences rather than of narratives. This area, called
the inferior frontal gyrus, or Broca’s area, helps distinguish
between “dog bites man” and “man bites dog”.
Harvard neurologists Aaron Berkowitz and Daniel Ansari showed that this pattern of activation is not just the case
for musical improvisation in jazz, but also for improvisation
in classical music. Instead of studying the brains of jazz musicians, they examined classical pianists’ brains in the same
improvisation-versus-non-improvisation setup. Berkowitz
and Ansari found that improvisational activations in classical musicians overlapped significantly with those observed
in jazz musicians4.
Siyuan Liu, a student of Allen Braun, furthered these
improvisational functional imaging findings by studying the
brains of freestyle rappers while performing a lyrical improvisation or a composed verse. He found that the main difference between improvised and rehearsed rap was activation
in the same narrative structure region as between improvised and rehearsed jazz, the medial prefrontal cortex5.
phrase structure suggests how certain notes and rhythms
would fit in the context of the previously played notes and
rhythms.
But where exactly is the line drawn between improvised
music and language in the brain?
Intuitively, one might suspect that although the structural elements of music and language are similar, different
strategies are used to assign meaning to them. For example,
following an A with an E flat in the key of C would be unlikely
in the same way that following “apple” with “are” would be
unlikely in English. However, the way in which we would
interpret the meaning of those two events is completely different: “apple” refers directly to something in the world; the
note A does not.
Steven Brown, a neuroscientist from the University of
Texas, used positron emission tomography to show exactly
that. He studied the brains of amateur musicians as they
vocally improvised with either music or language. He found
that the areas of the brain used for processing structure related to word or note ordering were largely the same, but
that they occurred on different sides—language on the left,
music on the right. The two kinds of improvisation did not
appear to share any neurological real estate directly related
to interpretation or meaning6.
Brown’s findings suggest that the same kind of neuro-
logical machinery produces the structural elements of both
musical and linguistic improvisation. Although the syntactic structure is processed similarly, whichever neurological
machinery endows music with meaning does not require an
ability to do the same for language. In other words, you do
not need to speak English to speak jazz. Perhaps this effect
is what an artist is referring to when she claims to express
herself more truly with her medium than with language. She
can articulate a story, but without being constrained by how
literally meaning is assessed in language.
Donnay, Limb, and their colleagues supported Brown’s
findings with their imaging study of trading. They observed
the right hemisphere activation, which is key for music, but
not language. However, they also observed musical improvisational activation in the language areas on the left side
of the brain, which Brown thought activated exclusively for
language. This suggests that not only do improvised music
and language rely on some of the same kinds of neurological
machinery, but that, as improvised music becomes increasingly conversational, the processing of musical structure
increasingly resembles the processing of linguistic structure.
Thelonious Monk plays piano at Minton's Playhouse in New York in
September 1947. Photograph by William P. Gottlieb.
Thelonious Monk, Howard McGhee, Roy Eldridge, and Teddy Hill
outside Minton’s Playhouse. Photograph by William P. Gottlieb.
NEUROLOGICAL DIFFERENCES BETWEEN
IMPROVISED MUSIC AND LANGUAGE
The brain is clearly using similar neurological mechanisms
when producing musical improvisation as when producing
language. The first kind of mechanism, in the medial prefrontal cortex, supports narrative structure. Musical narrative structure suggests how a given musical phrase fits into
the overall story—gradually introducing tension and building to a resolution. The second kind of mechanism, in the
inferior frontal gyrus, supports phrase structure. Musical
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INTERPRETATION OF MUSICAL IMPROVISATION
A team of German music physiology researchers led by
Eckhart Altenmüller used electroencephalography to com-
pare brain activations with reported enjoyment of listening
to certain songs. Participants listened to jazz, classical, and
popular songs, then rated how much they liked each song.
The best predictor of the listeners’ enjoyment of the music
was lateralization of their brain activation. If the left prefrontal cortex activated more than the right, the listener
probably enjoyed the song; if the right prefrontal cortex activated more than the left, then the listener probably did not
enjoy the song. This was the case across all genres7.
They also found that people tended to like the popular
songs, all of which had lyrics, more than the classical or jazz
songs, of which none had lyrics. This means that enjoyment,
lyrics, and left frontal cortex activation tended to appear together. The main exception to this trend is when participants
reported enjoyment when listening to either classical or jazz.
Their left frontal cortex activated even though there were
no lyrics. While there are many plausible interpretations of
these results, one possibility is that this left frontal cortex
activation in the absence of lyrics is the brain’s attempt to
impose narrative structure over the musical story. Those
who successfully imposed the narrative structure enjoyed
the music and experienced left frontal cortex activation;
those who failed to impose narrative structure did not enjoy
the music and showed no left frontal cortex activation.
Perhaps this explains how audiences began to enjoy
Monk. They tapped into the story that Monk was telling and
were able to interpret it for themselves.
This effect is similar to what happens when you know
what someone is going to say before they say it. You can
tell where the conversation is going, and you are tempted to
finish the speaker’s thought before he gets there. When listening to jazz improvisation, your brain can pick up on that
same anticipation of the next step. This anticipation draws
you in to the musician’s story. When an artist employs his
medial prefrontal cortex to create a melody that allows the
listener to engage her own narrative voice, that is when improvised music elates us.
The enjoyment of bebop is not exclusive to the rakish
lounges of 1940s New York. This phenomenon resonated
throughout the world. Bebop festivals are now held in many
major cities: from Cape Town to København, from Montréal
to Monterrey. Regardless of mother tongue, people pick up
on the storyline.
Though we can now begin to see how the brain makes
musical improvisation possible, it does not diminish our perception of its artistic beauty. In fact, it expands the beauty
of music by demonstrating the independence of improvised
music from cultural boundaries. As Herbie Hancock, director of the Thelonious Monk Institute of Jazz, said: “Music
truly is the universal language.”
By Cody Kommers
References on page 33
GREY MATTERS | vol 2 | issue 1
28
The Language of Music
The Language of Music
Image by Justin Waterhouse
MEMORY DISTORTION
Many storytellers have dealt with the topic of memory alteration. Public consensus
is that such stories are fanciful. It is typically believed that it is impossible to enter
someone’s mind to implant a memory that never occurred. What many people may not
realize, however, is that distortion of existing memories and creation of entirely false
ones are phenomena that have not only been observed in the real world, they have
actually been replicated in human test subjects.
MEMORY RECALL IS NOT PERFECT
It is well established that some experiences, such as stress,
can strongly disrupt memory formation and recall. In particular, glucocorticoids, a hormone released from the adrenal
glands, have an inhibitory effect on memory recall4.
In recent a study exploring human memory consolidation and recall in stressful conditions showed that high levels
of the glucocorticoid cortisol were significantly correlated
with poor performance on memory tasks7.
Human subjects in a “stressed” experimental group
were asked to participate in a mock job interview in front
of an audience of evaluators. In the middle of the interview,
they were suddenly asked to recall vocabulary from a word
association activity they participated in five weeks beforehand. The control group was simply asked to recall their
words with these stressors removed.
The stressed group, researchers found, had elevated levels of cortisol in their saliva, as well as increased heart rate
and blood pressures compared to control. Further, these
stressed subjects performed worse in recalling “negative”
word association vocabulary. However, it should be noted
that stressed subjects were equally able to recall “neutral”
word associations as non-stressed control.
THE “MISINFORMATION” EFFECT
Memory errors can extend beyond simply forgetting
words under stress. In a series of now classic experiments,
researchers have demonstrated that lasting and sometimes
dramatic memory errors can occur.
In one study participants watched a video in which a
traffic accident takes place near a stop sign. They then received a written summary of the accident and asked to recall,
FALSE RECOGNITION
FUNCTIONAL MAGNETIC RESONANCE IMAGING
Reporting recognition of an object that has not actually been
previously seen.
fMRI detects which portions of the brain are most active at any
given time by measuring changes in blood flow.
29
GREY MATTERS | vol 2 | issue 1
from memory, details about the video. If the summary substituted the stop sign for a yield sign, participants believed
they had viewed a yield sign in the video, somehow adopting
this into memory, in place of the stop sign that was actually
there4.
In a similar study, test subjects watched a video of a man
stealing a girl’s wallet, with the girl sustaining a neck injury
as a result. After watching the video, subjects were given a
summary of the events that had occurred on screen. However, subjects were told that the girl had hurt her arm instead
of her neck. When asked to recall the sequence of events in
the video at a later time, almost half (47%) of the test subjects not only recalled an arm injury taking place during the
sequence of events – they claimed to possess a visual memory of this occurrence2.
This susceptibility of memory to fabrication has been
called the “misinformation effect” by researchers. The sudden belief that one has seen something different than what
actually occurred, just because it was verbally stated, is striking to say the least.
jected to aggressive therapeutic techniques, even to the point
of taking hallucinatory “truth serum”, and then subsequently
claiming to have unearthed years of familial abuse. In one
such case, covered extensively by Time Magazine, a young
woman, after undergoing such therapy, sued her father for
years of sexual abuse, and also claimed to witness a murder
that he perpetrated1.
If a person can mentally replace a stop sign with a yield
sign, is it possible that she could remember witnessing a
murder that never actually occurred?
A variety of experiments, all with the same basic methodology, have shown that complex memories can be implanted.
The families of research participants were asked to
share the details of several meaningful events that occurred
during the participant’s childhood. The researchers then
met with participants and discussed their memories of each
event including one that the researchers had made up and
included in the list.
Although many subjects did not initially remember the
false memory - being lost at a shopping mall and returned to
their family by an elderly person - repeated questioning led
to about 30% of subjects reporting partial or even complete
memories of the ordeal2.
Being lost in a shopping mall is not an entirely unusual
experience. So, some skepticism of this finding is warranted. However, in several follow-up studies, researchers have
shown implanted memories that are fanciful, or even ridiculous. Participants have been led to believe and subsequently
“remember” that they spent the night at the hospital for low
blood sugar as children2, that they once attended a wedding
and spilled punch on the parents of the bride, or that they
fled a grocery store after the overhead sprinklers spontaneously activated1.
Participants in one study could even be made to believe
that they had proposed marriage to a Pepsi machine on a
college campus. If subjects either imagined themselves preforming this bizarre task, or witnessed someone else doing
so, they adopted the memory as their own within two weeks.
Subjects rated their confidence in having proposed to an inanimate object very highly6.
ARE FALSE MEMORIES EVER DISTINGUISHABLE?
Given that most people rely on their memory as an accurate
source of information, important questions have been raised
in response to this research. Is it possible to distinguish between an event that actually occurred, and one that did not?
Functional magnetic resonance imaging (fMRI) studies
of false memory show that the Para hippocampus and sensory cortex are more active during true memory recall (for
example: object recognition) than false5. Despite these differences in neural activity, conscious awareness of such false
memories is still beyond the individual. So, while a test subject might confidently “remember” seeing a specific object,
reduced activity in the Para hippocampus or sensory cortex
suggest that such recognition is false.
While perhaps this is surprising, researchers hypothesize that in instances of false object recognition, these “memory” pathways are not as actively stimulated as in the case
of true object recognition. Thus, generating less activity in
these brain regions. Hypothetically, this better match would
produce greater Para hippocampal activity, and a more active signal in an fMRI scan5.
CONCLUSION
Research into memory has made it clear that our recollecMALLEABILITY OF MEMORY/FALSE IMPLANTATION
tions are not always as dependable as we assume them to be.
Some researchers, in further exploring the misinformation Not only do studies suggest the ability to alter memories, but
effect, are trying to understand whether memory distortion to implant them altogether. Such findings challenge us to recan extend to complete fabrication. Altering a pre-existing think our understandings of the past, keeping the distortion
memory seems fundamentally different than creating one of memory in mind as we do so.
that never existed.
The possibility of implanted memories first generated
public interest in the late 20th century, when the psychotherapeutic practice of unearthing repressed memories
came into vogue. Prominent media outlets covered stories of
By Eva Alderman
citizens who had recently undergone therapy and were subReferences on page 33
GREY MATTERS | vol 2 | issue 1
30
Selective Visual Attention
Selective Visual Attention
SELECTIVE
VISUAL
ATTENTION
The tendency to overlook extraneous
information in our cluttered
visual environments is referred to as
selective attention.
In a popular demonstration video by Christopher Chabris
and Daniel Simons, viewers are asked to count the number
of times a team in white shirts passes a basketball. But as
they focus on the task, only half of the participants notice
something out of the ordinary1.
This tendency to overlook extraneous information in
our cluttered visual environment is referred to as selective
attention. It involves two basic but separate problems: information processing and information filtering. A fraction of
the information sent from the retina to the brain can be processed, and of what is processed, typically an even smaller
amount is attended to. As a result, people are primarily
aware of accentuated stimuli, leaving other objects to sit relatively unnoticed within their field of vision2.
In the aforementioned video, emphasis was placed on the
team in white, drawing attention to them. As a result, when
asked about the unattended stimulus (players in black), it
became significantly harder to recall what took place. Even
more striking, a majority of viewers completely miss the
giant gorilla that walks through the frame1.
Traditionally, selective visual attention has been assumed
to follow a “spotlight” model in which humans focus on processing one area in their visual field, and draw information
from that particular area3. Recent studies, however, have
presented strong evidence promoting a theory of competition where stimuli within the broader visual field “fight” for
limited working memory. Any stimuli out of the ordinary or
specifically looked for are then processed - eating up working memory - while the other extraneous information is left
unanalyzed.
FIGHTING FOR WORKING MEMORY
Due to the limited capacity of working memory, the
human brain is unable to simultaneously focus on a large
number of objects within its visual field. In a series of simple experiments that demonstrate this inability, two objects
are presented simultaneously in a visual field for a brief
moment4. Afterward, subjects are asked about some property of the objects, such as size, brightness, or shape.
Subject responses reveal crucial results. First, dividing
attention between two objects results in poorer performance
than focusing on just one. Second, processing is bottlenecked
at the level of stimulus input; showing one object after the
other with a slight delay results in much better performance4.
Finally, the ability to process stimuli is mostly unrelated to
the distance between the objects, suggesting humans do not
spotlight one area of their visual field to process information,
as previously supposed4.
These assertions were first established empirically by
To watch the basketball demonstration visit: www.greymattersjournal.com/gorilla
31
Image by Benjamin Cordy
Image by Benjamin Cordy
GREY MATTERS | vol 2 | issue 1
Donderi and Zelnicker in 1969 when they presented one target among a number of nontargets for a subject to identify3.
In the study, “easy” cases were distinguished from “hard”
ones. In easy cases, the target is clearly distinct from the
others (a white square among a number of black circles, for
example). Hard cases, on the other hand, featured targets
that shared a variety of properties with the nontargets (e.g.
having brightness, size, and shape in common).
In the easy cases, nontargets provide weak competition
for drawing attention toward them, as they are clearly distinct from the target itself. Given more factors in common,
however, it becomes significantly harder to pick out the
target over nontargets. This shows that the unconscious
bias towards uniqueness is just as important as purposefully-drawn attention in the visual field4.
BOTTOM-UP BIAS AND TOP-DOWN CONTROL
As alluded to before, the current model of selective visual
attention asserts that the targets and nontargets in a field
of vision compete for working memory5. The bottom-up bias
states that unique targets are easily identified among a number of homogeneous nontargets. Similarly, novel stimuli that
enter a field of vision attract attention, and therefore processing power. In this way bottom-up bias can be considered
to function as a series of largely automatic processes.
Bottom-up bias may be the result of nontargets being
stored in memory as the context or background - rather
than as a potential target. There may also be related biases
toward sudden appearances of new objects in the visual field,
or toward objects that are larger, brighter, or faster. In such
cases of stimulus-driven bias, the target seems to “pop out”
of the background of homogeneity2.
But just as target selection is dependent on bottom-up
bias, top-down control is needed to process the information
that is relevant to current behavior. For instance, attention
can be purposefully drawn to one property of a number of
shapes, or a discriminable colored target in a multicolored
display. Only when targets are not easily discriminable does
it become more difficult to distinguish between them and
nontargets5. In a given visual field, our attention is naturally
drawn to objects that stand out from the background in some
way, but it can also be artificially drawn to what we want to
focus on. When those two ideas conflict, such as when we are
looking for objects that do not stand out in our visual field,
they become harder to locate and distinguish5.
One question up for debate in this current model of selective attention is the reason behind competition for focus
within the brain. There are a few theories as to why this
might be. For one, it may be possible that full visual analysis
of every object in a scene would be too complex for the brain
to handle – thus competition between objects is a result of
limited identification capacity5. However, an equally strong
theory proposes that a lack of control over response systems
is the cause. Indeed, it was demonstrated by Eriksen and
Eriksen in 1974 that subjects’ attentions are drawn to objects
that they have specifically been told to ignore6. Regardless,
competition likely occurs at multiple levels between sensory
input and motor output7.
NEURAL PROCESSES
Objects within a visual field compete for processing in
a network of more than thirty cortical visual areas, which
are organized into two main corticocortical streams which
begin in the primary visual cortex (V1). From there, a ventral stream is projected into the inferior temporal cortex for
object recognition while a dorsal stream is projected into the
posterior parietal cortex for spatial perception and visuomotor performance. Both eventually are projected into the
prefrontal cortex8.
As competition involves object recognition, the ventral
stream is the key to selective attention.
The ventral pathway primarily includes the extrastriate
visual cortical areas V2 and V4, as well as TEO and ending
in TE in the inferior temporal cortex. As visual information
progresses through the ventral stream, the manner in which
that information is processed grows more and more complex. For instance, V1 neurons act as filters for both distance
and time, V2 neurons respond to visual contours, and inferior temporal neurons respond selectively to overall object
features8.
Additionally, the receptive field of visual neurons – the
area within a visual field that each neuron responds to –
increases at each stage. Moving down the pathway from V1
to V4 to TEO to TE, typical receptive fields are on the order
of 0.2, 3.0, 6.0, and 25.0 degrees in size respectively.
The receptive fields are seen as a crucial processing
resource that objects in the visual field compete for, and as
object features are coded into the ventral stream, the information available about any specific target declines as more
objects are added to receptive fields. As a means of focusing
attention, the visual system splits processing between the
targets, and relevance is assigned to objects through either
top-down or bottom-up processes to help decide which ones
to focus on9.
CONCLUSIONS
Although the human retina is bombarded by information, only a select amount is processed and acted upon. At
several instances between input and output, objects in the
visual field “compete” for limited processing power of the
ventral stream. The competition is biased by both bottom-up
and top-down processes. Thus visual attention is less like a
“spotlight” but rather as a series of interactions between the
objects themselves as they compete for processing.
By Darren Hou
References on page 33
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GREY MATTERS | vol 2 | issue 1
All Things Neuroscience
GREY MATTERS | vol 2 | issue 1
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Grey Matters Journal is funded, in part, by the generous support of the
departments of Pharmacology, Psychology, Physiology & Biophysics,
the Neurobiology major, and the College of Arts & Sciences at the
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