|Scientific American, february 2013.
By Rodrigo Quian Quiroga, Itzhak Fried and Christof Koch||
Brain Cells for Grandmother
Each concept - each person or thing in our everyday experience - may have a set of
corresponding neurons assigned to it
Tussentitel: A single neuron that responded to Luke Skywalker and his written
and spoken name also fired to the image of Yoda.
ONCE A BRILLIANT RUSSIAN NEUROSURGEON NAMED Akakhi Akakhievitch had a patient
who wanted to forget his overbearing, impossible mother.
Eager to oblige, Akakhievitch opened up the patient's brain and, one by one,
ablated several thousand neurons, each of which related to the concept of his
mother. When the patient woke up from anesthesia, he had lost all notion of his
mother. All memories of her, good and bad, were gone. Jubilant with his success, Akakhievitch turned his attention to the next endeavor - the search for cells
linked to the memory of "grandmother:"
The story, of course, is fiction. The late neuroscientist Jerry Lettvin (who,
unlike Akakhievitch, was real) told it to a crowd of students at the
Massachusetts Institute of Technology in 1969 to illustrate the provocative idea
that as few as about 18,000 neurons could form the basis of any particular
conscious experience, thought or memory of a relative or any other person or
object we might come across. Lettvin never proved or disproved his audacious
hypothesis, and for more than 40 years scientists have debated, mostly in jest,
the idea of "grandmother cells:' The idea of neurons that store memories in such
a highly specific manner goes all the way back to William James, who in the late
19th century conceived of "pontificial cells" to which our consciousness is
attached. The existence of these cells, though, runs counter to the dominant
view that the perception of any specific individual or object is accomplished by
the collective activity of many millions if not billions of nerve cells, what
Nobel laureate Charles Sherrington in 1940 called "a millionfold democracy:' In
this case, the activity of any one individual nerve cell is meaningless. Only
the collaboration of very large populations of neurons creates meaning.
Neuroscientists continue to argue about whether it takes relatively few
neurons-on the order of thousands or less-to serve as repositories for a
particular concept or whether it takes hundreds of millions distributed widely
throughout the brain.
Attempts to resolve this dispute are leading to new understanding of the
workings of memory and conscious thought-with a little help from Hollywood.
JENNIFER ANISTON NEURONS
SOME YEARS AGO- together with Gabriel Kreiman, now a faculty member at Harvard
Medical School, and Leila Reddy, now a researcher at the Brain and Cognition
Research Center in Toulouse, France-we performed experiments that led to the
discovery of a neuron in the hippocampus of one patient, a brain region known to
be involved in memory processes, that responded very strongly to different
photographs of actress Jennifer Aniston but not to dozens of other actors,
celebrities, places and animals. In another patient, a neuron in the hippocampus
lit up at the sight of pictures of actress Halle Berry and even to her name
written on the computer screen but responded to nothing else. Another neuron
fired selectively to pictures of Oprah Winfrey and to her name written on the
screen and spoken by a computer-synthesized voice. Vet another fired to pictures
of Luke Skywalker and to his written and spoken name, and so on.
This kind of observation is made possible by the direct recording of the
activity of individual neurons. Other more common techniques, such as functional
brain imaging, can pinpoint activity throughout the brain when a volunteer
performs a given task. Vet although functional imaging can track the overall
power consumption of typically a few million cells, it cannot identify small
groups of neurons, let alone individual cells. To record the electrical pulses
emitted by individual neurons, microelectrodes thinner than a human hair need to
be implanted in the brain. This technique is used less commonly than functional
imaging, and only special medical circumstances warrant implantation of these
electrodes in humans.
One of those rare circumstances occurs when treating patients
with epilepsy. When seizures cannot be controlled with medication, these
patients may be candidates for remedial surgery. The medical team examines
clinical evidence that can pinpoint the location of the area where seizures
start, the epileptic focus, which can potentially be surgically removed to cure
the patient. Initially this evaluation involves noninvasive procedures, such as
brain imaging, consideration of clinical evidence and the study of pathological
electrical activity-a multitude of epileptic discharges that all occur in
lockstep - with EEG recordings made from the patient's scalp. But when it is not
possible to accurately determine the location of the epileptic focus with these
methods, neurosurgeons may implant electrodes deep inside the skull to
continuously monitor in the hospital brain activity over several days and then
analyze the seizures observed.
Scientists sometimes ask patients to volunteer for research
studies during the monitoring period, studies in which a variety of cognitive
tasks are performed as brain activity is recorded. At the University of
California, Los Angeles, we have employed a unique technique to record within
the skull using flexible electrodes with tiny microwires; the technology was
developed by one of us (Fried), who heads the Epilepsy Surgery Program at U.C.L.A.
and collaborates with other scientists from around the world, including Koch's
group at the California Institute of Technology and Quian Quiroga's laboratory at
the University of Leicester in England. This technique furnishes an
extraordinary opportunity to record directly from single neurons for days at a
time in awake patients and provides the ability to study the firing of neurons
during various tasks-monitoring the incessant chattering that occurs while
patients look at images on a laptop, recall memories or perform other tasks.
That is how we discovered the Jennifer Aniston neurons and unwittingly revived
the debate ignited by Lettvin's parable.
GRANDMOTHER CELLS REVISITED
ARE NERVE CELLS such as the Jennifer Aniston neuron the long-debated grandmother
cells? To answer that question, we have to be more precise about what we mean by
grandmother cells. One extreme way of thinking about the grandmother cell
hypothesis is that only one neuron responds to one concept. But if we could find
one single neuron that fired to Jennifer Aniston, it strongly suggests that
there must be more-the chance of finding the one and only one among billions is
minuscule. Moreover, if only a single neuron would be responsible for a person's
entire concept of Jennifer Aniston, and it were damaged or destroyed by disease
or accident, all trace of Jennifer Aniston would disappear from memory, an
extremely unlikely prospect.
A less extreme definition of grandmother cells postulates
that many more than a solitary neuron respond to any one concept. This
hypothesis is plausible but very difficult, if not impossible, to prove. We
cannot try every possible concept to prove that the neuron fires only to
Jennifer Aniston. In fact, the opposite is often the case: we often find neurons
that respond to more than one concept. Thus, if a neuron fires only to one
person during an experiment, we cannot rule out that it could have also fired to
some other stimuli that we did not happen to show.
For example, the day after finding the Jennifer Aniston
neuron we repeated the experiment, now using many more pictures related to her,
and found that the neuron also fired to Lisa Kudrow, a costar in the TV series
Friends that catapulted both to fame. The neuron that responded to Luke
Skywalker also fired to Yoda, another Jedi from Star Wars; another neuron fired
to two basketball players; another to one of the authors (Quian Quiroga) of this
article and other colleagues who interacted with the patient at U.C.LA., and so
on. Even then, one can still argue that these neurons are grandmother cells that
are responding to broader concepts, namely, the two blond women from Friends,
the Jedis from Star Wars, the basketball players, or the scientists doing
experiments with the patient. This expanded definition turns the discussion
of whether these neurons should be considered grandmother cells into a semantic
Let us leave semantics aside for now and focus instead on a
few critical aspects of these so-called Jennifer Aniston neurons. First, we
found that the responses of each cell are quite selective-each fires to a small
fraction of the pictures of celebrities, politicians, relatives, landmarks, and
so on, presented to the patient. Second, each cell responds to multiple
representations of a particular individual or place, regardless of specific
visual features of the picture us ed. Indeed, a cell fires in a similar manner
in response to different pictures of the same person and even to his or her
written or spoken name. It is as if the neuron in its firing patterns tells us:
"I know it is Jennifer Aniston, and it does not matter how you present her to
me, whether in a red dress, in profile, as a written name or even when you call
her name out loud:' The neuron, then, seems to respond to the concept-to any
representation of the thing itself. Thus, these neurons may be more
appropriately called concept cells instead of grandmother cells. Concept cells
may sometimes fire to more than one concept, but if they do, these concepts tend
to be closely related.
A CODE FOR CONCEPTS
TO UNDERSTAND the way a small number of cells become attached to a particular
concept such as Jennifer Aniston, it helps to know something about the brain's
complex processes for capturing and storing images of the myriad of objects and
people encountered in the world around us. The information taken in by the eyes
first goes - via the optic nerve leaving the eyeball -t o the primary visual cortex
at the back of the head. Neurons there fire in response to a tiny portion of the
minute details that compose an image, as if each were lighting up like a pixel
in a digital image or as if they were the colored dots in a pointillist painting
by Georges Seurat.
One neuron does not suffice to tell whether the detail is
part of a face, a cup of tea or the Eiffel Tower. Each cell forms part of an
ensemble, a combination that generates a composite image presented, say, as A
Sunday Afternoon on the Island of La Grande Jatte. If the picture changes slightly,
some of the details will vary, and the firing of the corresponding set of neurons
will change as well.
The brain needs to process sensory information so that it
captures more than a photograph - it must recognize an object and integrate it
with what is al ready known. From the primary visual cortex, the neuron al
activation triggered by an image moves through a series of cortical regions
toward more frontal areas. Individual neurons in these higher visual areas
respond to entire faces or whole objects and not to local details. Just one of
these high-level neurons can tell us that the image is a face and not the Eiffel
Tower. If we slightly vary the picture, move it about or change the lighting
illuminating it, it will change some features, but these neurons do not care
much about small differences in detail, and their firing will remain more or
less the same-a property known as visual invariance.
Neurons in high-level visual areas send their information to
the medial temporal lobe-the hippocampus and surrounding cortex-which is
involved in memory functions and is where we found the Jennifer Aniston neurons.
The responses of neurons in the hippocampus are much more specific than in the
higher visual cortex. Each of these neurons responds to a particular person or,
more precisely, to the concept of that person: not only to the face and other
facets of appearance but also to closely associated attributes such as the
In our research, we have tried to explore how many individual
neurons fire to represent a given concept. We had to ask whether it is just one,
dozens, thousands or perhaps millions. In other words, how "sparse" is the
representation of concepts? Clearly, we cannot measure this number directly,
because we cannot record the activity of ail neurons in a given area. Using
statistical methods, Stephen Waydo, at the time a doctoral student with one of
us (Koch) at Caltech, estimated that a particular concept triggers the firing of
no more than a million or so neurons, out of about a billion in the medial
temporal lobe. But because we use pictures of things that are very familiar to
the patients in our research - which tend to trigger more responses- this number
should be taken strictly as an upper bound; the number of ceils representing a
concept may be 10 or 100 times as small, perhaps close to Lettvin's guess of
18,000 neurons per concept.
Contrary to this argument, one reason to think that the brain
does not code concepts sparsely, but rather distributes them across very large
neuronal populations, is that we may not have enough neurons to represent ail
possible concepts and their variations. Do we, for instance, have a big enough
store of brain ceils to picture Grandma smiling, weaving, drinking tea or
waiting at the bus stop, as well as the Queen of England greeting the crowds,
Luke Skywalker as a child on Tatooine or fighting Darth Vader, and so on?
To answer this question, we should first consider that, in
fact, a typical person remembers no more than 10,000 concepts. And this is not a
lot in comparison to the billion nerve ceils that make up the medial temporal
lobe. Furthermore, we have good reason to think that concepts may be coded and
stored very efficiently in a sparse way. Neurons in the medial temporal lobe just
do not care about different instances of the same concept-they do not care if
Luke is sitting or standing; they only care if a stimulus has something to do
with Luke. They fire to the concept itself no matter how it is presented. Making
the concept more abstract-firing to ail instances of Luke-reduces the
information that a neuron needs to encode and allows it to become highly
selective, responding to Luke but not to Jennifer.
Simulation studies by Waydo underscore this view even further.
Drawing on a detailed model of visual processing, Waydo built a software-based
neural network that learned to recognize many unlabeled pictures of airplanes,
cars, motorbikes and human faces. The software did so without supervision from a
teacher. It was not told "this is a plane and that a car:' It had to figure this
out by itself, using the assumption that the immense variety of possible images
is in reality based on a small number of people or things and that each is
represented by a small subset of neurons, just as we found in the medial
temporal lobe. By incorporating this sparse representation in the software
simulation, the network learned to distinguish the same persons or objects even
when shown in myriad different ways, a finding similar to our observations from
human brain recordings.
WHY CONCEPT CELLS?
OUR RESEARCH is closely related to the question of how the brain interprets the
outside world and translates perceptions into memories. Consider the famous 1953
case of patient H.M., who suffered from intractable epilepsy. AB a desperate
approach to try to stop his seizures, a neurosurgeon removed his hippocampus and
adjoining regions in both sides of the brain. After the surgery, H.M. could
still recognize people and objects and remember events that he had known before
the surgery, but the unexpected result was that he could no longer make new
long-lasting memories. Without the hippocampus, everything that happened to him
quickly fell into oblivion. The 2000 movie Memento revolves around a character
who has a similar neurological condition.
H.M's case demonstrates that the hippocampus, and the medial
temporal lobe in general, is not necessary for perception but is critical for
transferring short-term memories (things we remember for a short while) into
long-term memories (things remembered for hours, days or years). In line with
this evidence, we argue that concept ceils, which reside in these areas, are
critical for translating what is in our awareness-whatever is triggered by
sensory inputs or internal recall-into long-term memories that will later be
stored in other areas in the cerebral cortex. We believe that the Jennifer
Aniston neuron we found was not necessary for the patient to recognize the
actress or to remember who she was, but it was critical to bring Aniston into
awareness for forging new links and memories related to her, such as later
remembering seeing her picture.
Our brains may use a small number of concept cells to
represent many instances of one thing as a unique concept-a sparse and invariant
representation. The workings of concept cells go a long way toward explaining
the way we remember: we recall Jennifer and Luke in all guises instead of
remembering every pore on their faces. We neither need (nor want) to remember
every detail of whatever happens to us.
What is important is to grasp the gist of particular
situations involving persons and concepts that are relevant to us, rather than
remembering an overwhelming myriad of meaningless details. If we run into
somebody we know in a cáfé, it is more important to remember a few salient
events at this encounter than what exactly the person was wearing, every single
word he used or what the other strangers relaxing in the café looked like.
Concept cells tend to fire to personally relevant things because we typically
remember events involving people and things that are familiar to us and we do
not invest in making memories of things that have no particular relevance.
Memories are much more than single isolated concepts. A
memory of Jennifer Aniston involves a series of events in which she - or her
character in Friends for that matter - takes part.
The full recollection of a single memory episode requires links between
different but associated concepts: Jennifer Aniston linked to the concept of
your sitting on a sofa while spooning ice cream and watching Friends.
If two concepts are related, some of the neurons encoding one
concept may also fire to the other one. This hypothesis gives a physiological
explanation for how neurons in the brain encode associations. The tendency for
cells to fire to related concepts may indeed be the basis for the creation of
episodic memories (such as the particular sequence of events during the café
encounter) or the flow of consciousness, moving spontaneously from one concept
to the other. We see Jennifer Aniston, and this perception evokes the memory of
the TV; the sofa and ice cream-related concepts that underlie the memory of
watching an episode of Friends. A similar process may also create the links
between aspects of the same concept stored in different cortical areas, bringing
together the smell, shape, color and texture of a rose - or Jennifer's appearance
Given the obvious advantages of storing high-level memories
as abstract concepts, we can also ask why the representation of these concepts
has to be sparsely distributed in the medial temporal lobe. One answer is
provided by modeling studies, which have consistently shown that sparse
representations are necessary for creating rapid associations.
The technical details are complex, but the general idea is
quite simple. Imagine a distributed-as opposite of sparse-representation for the
person we met in the café, with neurons coding for each minute feature of that
person. Imagine another distributed representation for the café itself. Making a
connection between the person and the café would require creating links among
the different details representing each concept but without mixing them up with
others, because the café looks like a comfortable bookstore and our friend looks
like somebody else we know.
Creating such links with distributed networks is very slow
and leads to the mixing of memories. Establishing such connections with sparse
networks is, in contrast, fast and easy. It just requires creating a few links
between the groups of cells representing each concept, by getting a few neurons
to start firing to both concepts. Another advantage of a sparse representation
is that something new can be added without profoundly affecting everything else
in the network. This separation is much more difficult to achieve with
distributed networks, where adding a new concept shifts boundaries for the
Concept cells link perception to memory; they give an
abstract and sparse representation of semantic knowledge - the people, places,
objects, all the meaningful concepts that make up our individual worlds. They
constitute the building blocks for the memories of facts and events of our
lives. Their elegant coding scheme allows our minds to leave aside countless
unimportant details and extract meaning that can be used to make new
associations and memories. They encode what is critical to retain from our
Concept cells are not quite like the grandmother cells that Lettvin envisioned,
but they may be an important physical basis of human cognitive abilities, the
hardware components of thought and memory.
For decades neuroscientists have debated how memories are stored. That debate
continues today, with competing theories-one of which suggests that single
neurons hold the recollection, say, of your grandmother or of a famous movie
The alternative theory asserts that each memory is distributed across many
millions of neurons. A number of recent experiments during brain surgeries
provide evidence that relatively small sets of neurons in specific regions are
involved with the encoding of memories.
At the same time, these small groupings of cells may represent many instances of
one thing; a visual image of Grandma's face or her entire body-even a front and
side view or the voice of a Hollywood star such as Jennifer Aniston.
To Code a Memory
Neuroscientists ardently debate two altemative theories of how memories are
encoded in the brain. One theory contends that the representation of a single
memory-the image of Luke Skywalker, for instance-is stored as bits and pieces
distributed across millions or perhaps billions of neurons. The altemative view,
which has gained more scientific credibility in recent years, holds that a
relatively few neurons, numbering in the thousands or perhaps even less,
constitute a "sparse" representation of an image. Each of those neurons will
switch on to the image of Luke, whether from a distance or close-up.
Some but not al! of the same group of neurons will also flre to the related
image of Yoda.
Similarly, a separate set of specifJc neurons activates wh en perceiving
More to explore
Sparse but Not "Grandmother-Cell" Coding in the Medial Temporal Lobe. R. Quian
I Quiroga, G. Kreiman, C. Koch and I. Fried in Trends in Cognitive Sciences,
Vol. 12, No. 3, pages 87-91; March 2008.
Percepts to Recollections: Insights from Single Neuron Recordings in the Human
Brain. Nanthia Suthana and Itzhak Fried in Trends in Cognitive Sciences, Vol.
16, No. 8, pages ~ 427-436; July 16, 2012.
Concept Cells: The Building Blocks of Declarative Memory Functions. Rodrigo Quian I Quiroga in Nature Reviews Neuroscience, Vol. 13, pages 587-597; August
SCIENTIFIC AMERICAN ONLINE Read an excerpt of Quian Quiroga's book on memory
Itzhak Fried is a professor of neurosurgery and director of the Epilepsy Surgery
Program at the U.C.LA David Geffen School of Medicine. He is also a professor at
the Tel Aviv Sourasky Medical Center and Tel Aviv University.
Rodrigo Quian Quiroga, a native of Argentina, is professor and head of the
Bioengineering Research Group at the University of Leicester in England. He is
author of the recently published Borges and Memory:
Encounters with the Human Brain (MIT Press, 2012). r
Christof Koch is professor of cognitive and behavioral biology at the Califomia
Institute of Technology and chief scientific officer at the Allen Institute for
Brain Science in Seattle.
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