r e S e a r C H a n d i n n o V a T i o n a T T H e u n i V e r S i T Y o F T o r o n T o • w i n T e r 2 0 1 3 • V o l . 1 5 , n o . 1

The Brain Issue

BRAINexPlorerSThe quest to understand what makes us human

Baycrest researcher jennifer Ryan: understanding memory through eye movement monitoring.

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THE BRAIN ISSUE

How did a weak-jawed, slow-moving, featherweight of a primate

climb to the pinnacle of the food chain? How did these slightly-

built bipeds turn their most deadly predators into prey? How did

this frail species come to dominate desert, jungle and tundra —

the harshest climates on the planet?

It’s all thanks to the 1.3 litres of neurons and chemicals that

make up the human brain. Human intelligence was an evolution-

ary shift like no other, allowing us to overpower claws and fangs,

withstand freeze and flood, and survive famine and disease.

A human being has a body mass similar to that of an antelope,

but our brains are 10 times as large, and they use a fifth of our met-

abolic energy. We learn, solve problems, create and process infor-

mation with unmatched speed and flexibility. Even our closest

living relatives, bonobos and chimps, don’t come close.

Details are sketchy about the state of affairs three million (or so)

years ago when our ancestors’ brains started to change. It appears,

though, that the very products of human intelligence that make

us so powerful — use of tools, complex social structures and lan-

guage — were also the exact forces that created the modern brain.

“There’s feedback between technological change and devel-

opments in the brain,” says paleoanthropologist David Begun. “As

technology develops, it becomes increasingly valuable as a sup-

port mechanism. Technology becomes the selective agent, rather

than the environment.”

In other words, there was a shift in human evolutionary history

after which a superior brain became more important to survival

and reproduction than the ability to run, climb or throw a punch.

Once natural selection started favoring those who could use a

weapon, build a fire, tie a knot or forge an alliance, our evolutionary

course was set.

“It wasn’t a punctuated event,” says Begun. “We see over time

a gradual increase in brain size, both in absolute terms and relative

to body size.”

Somewhere around two million years ago, though, came a turn-

ing point: intelligence went from being merely valuable to being

essential. The species could no longer survive without technology.

Even as our brains were getting bigger and more complex, our

jaws and biceps were receding.

“Once you lose the very powerful chewing apparatus, you are

dependent on tools to process food,” Begun says.

The same goes for hunting and gathering, and for defense from

predators and the elements. As our brains became more sophisti-

cated, so did our language and culture. We developed spoken and

written language, art, systems of government, music, science, phi-

losophy, morality, religion, hobbies, humour and romance. Every

new facet the human brain fed back into the evolutionary cycle,

making this amazing organ that much more valuable to subse-

quent generations.

This process continues, and is, in fact, accelerating.

Every technological epoch — from the Stone Age to the Infor-

mation Age, is superseded more quickly than the last. And at each

stage, our brains become more central to survival.

Nobody knows if or when the human brain will reach the peak

of its ascension. From ancient weapons to particle accelerators to

the brain itself, we are still finding new ways to understand and

exploit our world. One thing is certain: the journey isn’t over yet.

Rise of the planet of the humansAnthropologist David Begun explains how our brains evolved by Patchen Barss

David Begun has been a

professor in the Department

of Anthropology at U of T

since 1989. He holds a PhD

in Paleoanthropology from

the University of Pennsyl-

vania. A frequent media

commentator, he is currently

editor of the Journal

of Human Evolution. His

book, The Real Planet of

the Apes, will be published

by Princeton University

Press in 2013.

THe Brain THen and nowIL

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2 E D G E / W I N T E R 2 0 1 3

Brain exploration offers powerful possibilitiesPROFESSOR R. PAUL YOUNG

when we think of explorers,

it is usually someone

like Ferdinand Magellan

finding his way around

the world by way of the

oceans, or aboriginal peo-

ples travelling across the former land bridge in the far

north into what we now know as North America, or

even astronauts flying far into the skies above us.

We understand exploration well from these

perspectives.

The brain, however, doesn’t have the vastness of

the continents, or the oceans, or outer space. Still, the

brain is very much like undiscovered territory, holding

mysteries that have fascinated researchers in myriad

fields for years.

You will meet some of the University of Toronto’s

leading brain explorers in this special issue.

Given the size of our research community — with

5,000 full-time scholars and researchers and the incred-

ible breadth they study — it is always a challenge to

represent them all in an issue of Edge.

But this issue on the brain presented a particu-

lar challenge. If the brain is what makes us human,

then it can be said that every professor at U of T has

something intelligent to say about the how the brain

works, what it is capable of, and how it can be repaired.

Indeed, this issue of Edge could literally be hundreds of

pages in length.

In the 12 pages that make up this issue, you will still

meet an impressive array of brain explorers — educa-

tors, neurosurgeons, psychiatrists, psychologists, reli-

gion scholars, anthropologists, computer scientists and

philosophers who are examining everything from how

children learn to why the human brain developed reli-

gion to fascinating work on repairing damaged brains

through a procedure called “deep brain stimulation.”

And we cap it off on page 12 with an interview

with Professor Donald Stuss, founding director of the

renowned Rotman Research Institute at Baycrest, a

scientist who conducted breakthrough work on the

role of the frontal lobe and who is now the CEO of

the Ontario Brain Institute.

True explorers all, searching for new knowledge

about one of our most complex challenges.

I hope you enjoy this issue.

Professor r. Paul Young, Phd, FrSC

Vice President, research and innovation

It took nature more than two billion years of incremental change

to get from the first complex cells to the sophisticated thinking

machine that is the human brain. Artificial intelligence researchers

have covered much of that same ground in under a century.

Digital brains continue to gain on people.

Just in the past year, artificial neural networks took a big leap

forward in their ability to recognize objects — one of the basic

skills necessary to understand the world.

Today, a person and a computer who are flashed the same

image have similar accuracy rates at identifying its content, though

the person wins if she can move her eyes to focus on different

parts of the image.

Quick object recognition, though, is just a small component of

human intelligence.

“The thing that is special about people is recursion. We’re good

at instant vision and recognition, but we’re excellent at putting

those instants together,” says computer science professor Geoffrey

Hinton. “The neural net people haven’t gotten very far with the

sequential aspect of it — putting together those rapid glimpses

into a coherent whole.”

You look at a tree. You think, “It’s a tree.” Then the interesting

part happens: your neurons and signaling pathways subtly

shift — feedback messages shoot back and forth, and neural

patterns change.

Experiencing that tree alters your overall understanding of the

world, better preparing your brain to interpret the next sensory

experience. This adaptive “learning algorithm” is what allows us to

have complex intelligence.

“Suppose I grow a plant in a flowerpot with a very complicated

internal shape. Then I remove the flowerpot, leaving a root system

with that same shape. Where did that complexity come from?

All you need is an adaptive algorithm in the plant’s DNA that

tells it to fill up space,” says Hinton. “It’s similar with the brain:

a simple and very powerful learning algorithm creates complicated

knowledge structures by adapting to complex structure

in the external world.”

In nature, such an algorithm developed through gradual

change over thousands of generations. Researchers aren’t limited

to such a process — they can look for solutions in places evolution-

ary biology couldn’t go. It turns out, though, that nature’s model

provides the most promising results.

“Curiously, making an artificial neural network similar to the

brain appears to make it work better,” Hinton says. “It doesn’t have

to be the case, but for perception, it seems to be.”

Hinton doesn’t speculate on when computers will make the

leap that humans made millions of years ago — a learning algo-

rithm that efficient is still some way off.

“We’re still trying to match the intelligence of cats and pigeons,”

he says.

Mammals and birds, though, only emerged 200 million years

ago — they represent the last 10 per cent of the evolutionary arc.

Neural networks and the computers on which they run are still in

their infancy.

What happens when we use our brains to create equally pow-

erful artificial brains? Even Hinton agrees that we might find out in

our lifetime.

The brain in the machineGeoffrey Hinton is chasing a learning algorithm to make machines think like us by Patchen Barss

Geoffrey Hinton won the

2012 Killam Prize for

Engineering and the 2010

Gerhard Herzberg Gold

Medal for Science and Engi-

neering for his contributions

to machine learning and

artificial intelligence. Hinton

joined U of T in 1987 after

stints at Sussex University, the

University of California San

Diego and Carnegie Mellon

University. He has a PhD from

the University of Edinburgh.

3E D G E / W I N T E R 2 0 1 3

They say eyes are windows to the soul — turns out they might be windows to the

brain, too.

Eye movements, says Jennifer Ryan of U of T and Baycrest, can tell us a lot about

how the brain is — or is not — working as we get older.

An associate professor of psychology and psychiatry at U of T and senior scientist

and academic director at Baycrest’s Rotman Research Institute, Ryan is interested in

how memory works and what parts of the brain are involved.

“I’m interested in understanding memory as a series of relations we put together,”

she says. A face might trigger a name, for example. Or passing a restaurant might

remind you that you celebrated your last birthday there.

Using eye movement monitoring, Ryan has shown that as we age, our ability to

make these kinds of relational memories declines.

“If you walked into my offi ce and saw an object that isn’t traditionally in an offi ce

— say there was a blender on my desk — your eyes would go to that unexpected

object faster than to other items in the room. That’s because of the knowledge and

memories you bring to the situation. You know the blender doesn’t belong.”

Ryan has shown that older people don’t make the same kind of eye movements as

younger ones, even though the mechanics of eye movements don’t change with age.

“If you ask people to remember the location of three objects on a table, younger adults

will transition between the three objects quite a bit with their eyes. Older adults won’t—

they’ll look at one longer, then move to another one. Later, if I take all the

objects away, the older adults will have trouble remembering what was where.”

When Ryan asks older adults to consciously move their eyes faster

among the objects, she fi nds their memory improves. She uses neuroimag-

ing to correlate eye movements with brain activity and hopes to develop

strategies to boost memory.

Ryan came to her interest in memory from an unusual source. “I used

to watch soap operas with my grandmother and mom and everyone has

amnesia on a soap at one point or another. I thought it was fascinating

and wondered if it could happen like that.”

Today, some of her research participants are amnesiacs. The kind of

amnesia that Ryan studies comes from a loss of oxygen to the brain,

a tumour or an epileptic episode (the soap opera version, it turns out,

doesn’t really exist) and they don’t involve a complete loss of memory.

These patients sometimes succeed at tasks they shouldn’t be able to,

given which areas of their brains are damaged. Ryan wants to know why

— and to fi gure out if the strategies they use can be transferred to condi-

tions like Alzheimer’s.

Even though the soaps exaggerated the condition, Ryan never lost

her curiosity about amnesia and the brain. Today she holds the Canada

Research Chair in the Cognitive Neuroscience of Memory. But, she says,

it was when she was interviewed by Soap Opera Digest that her family

was really impressed.

Jan Pelletier can explain how kids learn by telling a story about cockroaches.

Pelletier is a Canadian leader in the education and early development of children.

A former elementary school teacher and school psychologist, she is director of the

Dr. Eric Jackman Institute of Child Study (ICS) and a professor at U of T’s Ontario Institute

for Studies in Education (OISE).

The ICS has a three-fold mandate — research, teacher-researcher training and operation

of a renowned laboratory school for 200 children from nursery school to Grade 6. And it

is in this school where ICS researchers, teachers and student teachers aim to improve on

traditional models of how children learn.

That’s where the cockroaches come in.

“In our Grade 4 class, the teacher once had Hissing Madagascar Cockroaches in an aquar-

ium. She didn’t say to the students, ‘This is what their exoskeleton is like and this is how they

eat.’ Instead, she got them to form ‘inquiry groups’, and let them learn by asking questions. One

child wondered if they could teach the cockroaches to negotiate a maze, for example. Later,

they posted their theories on a hybrid learning discussion site called Knowledge Forum and

they built on each other’s theories. They sent e-mails with their observations to U of T ento-

mologists and analyzed the responses together. This is what we call ‘knowledge-building.’ It’s a

huge piece of the learning process. Children are naturally curious, so the best way to help them

learn is to let that curiosity rise.”

Pelletier points to a core set of other factors:

Security: “It’s important for young children to feel safe, in their home life, in their social

lives and at school,” says Pelletier. “Without a solid feeling of safety and security, they may be

less motivated or unable to capitalize on their curiosity. This comes from a long line of research

around the need for ‘secure attachment’ between children and parents. It starts when they are

babies and they give out signals, anticipating their parents’ response. As the parent or caregiver

continues to respond in a sensitive way, an attachment is formed. This process, called ‘serve and

return’ is the basis of the sense of security young children need for later learning.”

It’s OK to be wrong — especially when you have a great teacher: “We had one class dis-

cussing how leaves change colour on trees. One child said, ‘The clouds get too heavy and

dump a lot of rain on the tree and then the leaves have to protect themselves.’ That idea may be

wrong — but that’s OK. Some people worry that we’re letting children purposely do the wrong

thing. But gradually with a skilled educator, we bring the children to a more logical understand-

ing. Just think how much deeper your learning is when you have discovered it for yourself with

the guidance of a great teacher. Because you started it yourself, you remember it better.”

Home and school: “There has to be a connection between the parent and the school. Take

literacy, for example. Teachers can share their knowledge of helping a child to learn vocabu-

lary. And parents can take those tips home. My graduate students and I developed a program

on family literacy. Parents and children come for pizza once a week for nine weeks. It gives

mum and dad a night off cooking and we stage parent and child learning and related activities

around key concepts in literacy. This sharing of learning is often life-changing for children.

“I know how tough it is for parents to engage in their children’s learning. Parents are busier

than ever before and society is more frenetic. But, there is more understanding among research-

ers and the general public that early child development is absolutely critical to our future.”

The eyes have itJennifer Ryan monitors eye movements to understand how memory works by Jenny Hall

How do kids learn?Educator Jan Pelletier says it begins with their natural curiosity by Paul Fraumeni

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THE BRAIN ISSUE THINKING AND DOING

Jan Pelletier, left, with students at oiSe’s laboratory school.

Jennifer Ryan wears the Eye link iii, a head-mounted video eye tracker that gives researchers insight into how memory works.

4 E D G E / W I N T E R 2 0 1 3

what makes a mother? Alison Fleming, a behav-

ioural neuroscientist and professor of psychology

at the University of Toronto Mississauga, has spent

three decades asking this question. She’s carried

out dozens of experiments over 30 years, trying to

understand what’s on mothers’ minds — literally.

Fleming began her career investigating the psy-

chological changes mother rats undergo as a result

of pregnancy hormones. She later became interested

in identifying which parts of the brain were involved

in the psychological changes she observed.

“In a new rat mother you see a very rapid pro-

liferation of cells in the hippocampus that migrate

to various places elsewhere in the brain,” she says.

The mother’s dendrites — thread-like extensions of

neurons that receive electrochemical stimulation —

become more complex when a she’s interacting with

her babies. “We found through a variety of experi-

ments that a part of the brain called the amygdala is

also very important for mothering.” In rats that had

never given birth she found that this part of the brain,

which mediates emotion, was inhibited. In mothers,

hormones worked to remove that inhibition.

Later, she started looking at humans. “I began

thinking about how mothering is so complicated.

Mothers undergo not just hormonally-regulated

changes in mood, but also changes in cognition —

how they think, pay attention, remember and plan. We call this executive function.”

Fleming’s main focus today is on the long-term effects of mothering. “How you are

mothered yourself influences your neurotransmitters, neurogenesis, emotion and

executive function.” It even shapes what kind of mother you will be to your own kids.

Sound like a lot of pressure? No need to worry: Fleming says there is no one right

way to mother.

“On the extremes,” she concedes, “there can

be bad mothering. Harming a baby, for example, is

definitively bad. But there is huge variation in the

way that people interact with babies. If you look

cross-culturally, what would be considered optimal

mothering in one culture would not be in another.

Some cultures, like ours in North America, believe in

autonomy and individual development. Other cul-

tures think that interdependence is what matters,

so the way women mother is different. For example,

they might strap their babies to them. But one way

isn’t better than the other.”

Fleming stresses that “biology is not destiny.”

Early experiences of being mothered combine with

all kinds of inputs ranging from genetic to nutri-

tional to social to shape a person. Scientists are just

beginning to untangle these factors.

In fact, “mothering” doesn’t even have to

come from a mother. Fleming once gave female

rats that had never given birth newborn rat pups

to care for. Initially they rejected the pups, some-

times even going so far as to bury them. But after

about five days, they started acting like mothers,

licking their “babies” and adopting nursing pos-

tures even though they didn’t have any milk.

Human studies by Fleming and others have

shown the same effect: hormones might “turn on”

mothering in rats’ brains or “prime” it in humans, but sensory input, usually in the

form of exposure to a baby over time, can create the same outcome — a compulsion

to nurture — in both men and women.

“The brain mechanisms are in place in everyone,” she says. “I don’t believe that

the only person who can raise a child is a mother. It’s really about being attuned and

sensitive and responsive.”

The mind of a motherAlison Fleming investigates the causes and effects of maternal behaviour by Jenny Hall

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5E D G E / W I N T E R 2 0 1 3 5

Deep brain stimulation:how far can it go?Pioneering neurosurgeon Andres Lozano achieved groundbreaking results using a landmark surgical procedure on Parkinson’s and depression. Now he’s trying it on Alzheimer’s by Mark Witten

THE BRAIN ISSUE REPAIRING THE BRAIN

6 E D G E / W I N T E R 2 0 1 3

in 2003, neurosurgeon Dr. Andres Lozano was performing an experimental procedure designed

to suppress the appetite of a 53-year-old, 420-pound man with a lifelong history of obesity. When

Lozano switched on electrodes surgically implanted in the hypothalamus, a brain area that controls

hunger, the patient suddenly remembered a visit to a park with his girlfriend 30 years earlier. As the

electrical stimulation increased, the details became more vivid, and he could recall colours, sounds,

smells and the dress she was wearing.

“It happened by accident and I knew we were onto something important,” says Lozano, a pro-

fessor of surgery at the University of Toronto and Canada Research Chair in Neuroscience.

Using a technique known as deep brain stimulation (DBS), Lozano had serendipitously activated

the fornix, a bundle of nerve fibres that is the main highway in and out of the brain’s memory circuit.

Further tests after surgery revealed the patient’s verbal memory was much sharper when the stim-

ulation was turned on compared to when it was off. “His ability to remember words went through

the roof,” says Lozano, who decided to perform the identical procedure on six patients with mild

Alzheimer’s in a research study. The results from the first small trial of this experimental treatment

show promise in reversing the trajectory of an incurable brain disease that affects 500,000 Cana-

dians and five million North Americans.

Deep brain stimulation uses tiny electrodes implanted in specific brain regions to alter abnormal

brain activity and repair malfunctioning brain circuits. In Parkinson’s disease, for example, electrodes

are placed in areas responsible for body movement to repair the activity in the brain’s damaged

motor circuit. Small electrical pulses from a device similar to a cardiac pacemaker block the abnor-

mal firing of brain cells in Parkinson’s, caused by a lack of the brain chemical dopamine, and replace

it with a more regular pattern of

signalling that can dramatically

reduce motor symptoms such as

tremors, stiffness and gait prob-

lems. By stimulating a sweet spot,

the therapy alters the signalling

pattern across millions of inter-

connected cells in different brain

regions throughout the circuit.

Today, there is growing

excitement about the poten-

tial benefits of applying a ther-

apy that has safely reduced symptoms and improved quality of life for over 90,000 people with

movement disorders like Parkinson’s. Lozano, who pioneered the use of DBS for Parkinson’s in

North America and has treated over 800 patients at the University Health Network’s Toronto

Western Hospital, is in the forefront as the first neuroscientist to test and show promising results

in targeting the brain’s mood circuit for depression and memory circuit for Alzheimer’s.

He and others in the field are also exploring the use of DBS in trials as a treatment for epi-

lepsy, obsessive compulsive disorder, bipolar disorder, chronic pain, Tourette’s syndrome

and severe anorexia. “A large number of neurological and psychiatric disorders are not well

addressed despite our best drug therapies. We’re dealing with big problems, devastating dis-

eases where a bold approach is needed,” says Lozano, holder of the Dan Family Chair in Neuro-

surgery at U of T and the RR Tasker Chair in Functional Neurosurgery at UHN.

In a groundbreaking study published in Neuron in 2005, Lozano and neurologist Dr. Helen

Mayberg (formerly at U of T and now at Emory University) reported that four of six patients who

were considered untreatable showed a striking reduction in depression symptoms six months

after starting DBS treatment. Some had previously attempted or considered suicide. Lozano

recalls the amazing transformation in one patient during the procedure. “To our surprise, as

soon as we turned on the stimulator the depression went away. Her mood improved, and she

became engaged and interactive,” he says.

By placing electrodes in Broadmann Area 25, a sadness centre in the cerebral cortex, and con-

tinuously stimulating it with electricity, the doctors had turned down hyperactivity in the brain’s

sadness centre and boosted activity in the frontal lobes, restoring balance to the mood circuit in

these severely depressed patients.

In a follow-up study of 20 patients at U of T, UBC and McGill, about two-thirds improved sig-

nificantly. “Some of them are working, some are leading a normal life and some went into com-

plete remission. If patients respond to the treatment within three months, they tend to respond

over the long term,” says Lozano, who is now leading a phase 3 trial involving 200 patients at

18 North American medical centres. If proven safe and effective, DBS could be approved by the

FDA and Health Canada as an evidence-based therapy for major depression.

After following six Alzheimer’s patients treated with DBS for a year, he observed that the

memories of the two with the mildest symptoms got better and two stayed the same rather

than getting worse. Imaging showed DBS stimulated brain activity in their memory circuits.

“You can see that areas of the brain, like the temporal and parietal lobes, are lighting up. In

Alzheimer’s, these areas are shut down and use less glucose than normal, as if they are affected

by a power failure in the circuit. Deep brain stimulation restarts some of the shut down areas

and if we restore brain function, we expect patients to improve,” explains Lozano.

Even more remarkably, MRI

scans revealed one patient had

an eight per cent increase in the

hippocampus, the brain’s memory

hub, and another had a five per

cent increase. “That’s incredible. In

Alzheimer’s, the memory areas of

the brain shrink and we’ve never

seen the hippocampus grow,”

says Lozano, who then applied

DBS to this circuit in rodents and

found it increased the growth of

new brain cells by two to three times. “The rats that make more neurons get smarter and have a bet-

ter memory. We wonder whether this could be happening with the two Alzheimer’s patients.”

A phase 2, multi-centre trial is now underway in which 50 Alzheimer’s patients will have elec-

trodes implanted in their brains, but only half will have the stimulation turned on immediately.

In the others, it will be turned on in a delayed fashion. This will allow Lozano and his research

collaborators to compare and contrast the results in memory performance and brain structure.

“The clock is ticking in patients with Alzheimer’s. We’ve shown in the lab and in a small num-

ber of patients that electrical stimulation can change the structure of the brain and grow the

hippocampus. We’re upgrading the hardware of the brain and it may mean we could influence

the course of the illness,” he says.

Lozano is expanding the scope of DBS into a vast frontier of formidable diseases for which

there have been, until now, few hopes or effective treatments. “Deep brain stimulation is being

tested and used to treat conditions where we’re stuck. We can place electrodes anywhere in the

brain. It’s like exploring space. There is so much that’s unknown and so much to discover. That’s

where the excitement is,” he says.

STimulaTing a Brain To rePair iTSelF aFTer STrokeMolly Shoichet of the Department of Chemical Engineering &

Applied Chemistry and the Institute of Biomaterials and Bio-

medical Engineering is finding innovative regenerative medicine

strategies to overcome disease in the central nervous system,

including traumatic injury to the

brain, such as stroke.

Taking advantage of the plas-

ticity in the brain and its resident

neural stem cells, Shoichet and her

team, in conjunction with Cindi

Morshead from U of T’s Department

of Surgery and Dale Corbett

from the University of Ottawa’s

Faculty of Medicine, are investigating

minimally-invasive techniques to stimulate these particular stem

cells to achieve brain repair.

“The stroke itself stimulates these cells, but insufficiently to pro-

mote repair. By the co-delivery of two growth factors at specified

times, we’ve demonstrated enhanced tissue repair,” says Shoichet.

A Band-Aid-like method applied directly to the brain is being

tested. By injecting a drug delivery vehicle directly to the brain of ani-

mal models, Shoichet has been able to circumvent the blood-brain

barrier that prevents most molecules from diffusing into the brain.

“The exciting results from our research pave the way for

future studies in larger animal models where rehabilitation and

an enriched environment will further promote plasticity in the

brain. The ultimate goal for us is to test these innovative strate-

gies in humans,” says Shoichet. —Jennifer Hsu

BETTER—AND CHEAPER—BRAIN imaging For ePilePSY and STrokeBrain imaging. It calls to mind massive MRI machines or CT scan-

ners, with a patient immobilized while the machine does its work.

What if you could go about your daily life while a machine

you hardly noticed took images of your brain? It might not be so

far off, if Ofer Levi of the Institute

of Biomaterials and Biomedical

Engineering and the Department

of Electrical and Computer Engi-

neering has his way. He’s devel-

oping a low-cost, portable optical

imaging system to monitor brain

dynamics in patients with epilepsy,

stroke and traumatic brain injury.

Current techniques, Levi

says, “are large systems such as MRI or CT that are the size of

a room. You have to be immobile. You can’t leave a patient

more than an hour in them.” Optical technologies, on the other

hand, offer portable solutions. “You can walk around, and you

can be awake,” which gives a much more accurate picture of

brain activity.

They’re also potentially much less expensive. His team has

developed a 40-gram working prototype they’re testing on rats,

who carry the equipment around in backpacks. It’s built with the

sorts of lasers you find in an optical computer mouse and the

cameras found in a cell phone.

Once proven, it’s hoped the technique will allow doctors to

monitor the brain dynamics of human patients over a long period

of time—on the order of days, rather than the hour or so allowed

by current technology. —Jenny Hall

PROBING THE BRAIN’S RECOVERY MECHANISMS AFTER TRAUMATIC INJURY Whether caused by a car crash, a fall or some other incident,

traumatic brain injury can be debilitating. Cognitive functions

like memory and language are often impaired. So are motor

skills such as coordination and balance. Robin Green is trying

to better understand how these

functions recover.

A professor in the Department

of Psychiatry, a senior scientist at

Toronto Rehab and the Canada

Research Chair in Traumatic Brain

Injury, Green is examining the

idea that there is “competition”

between recovery of cognitive and

motor functions after traumatic

brain injury. In other words, the more one of these areas rec overs,

the less the other one does. This may be because injured

parts of the brain must compete for the limited neural resources

that support recovery following injury. Preliminary findings

support the hypothesis.

A second avenue of research is whether traumatic brain injury

is actually a progressive disorder. Green has shown that long after

the acute events of brain injury have resolved, grey matter contin-

ues to atrophy, white matter integrity is lost and lesions expand.

Her lab has found that there is less deterioration when people

receive more cognitive stimulation early on. This finding appears

to contradict the first. However, if cognitive stimulation (or “envi-

ronmental enrichment”) is creating new neural resources, then the

two sets of findings make sense. Her group is currently embarking

on a multi-pronged treatment research study to offset deteriora-

tion and enhance clinical outcomes. —Toronto RehabPHO

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“ we’re dealing with big problems, devastating diseases where a bold approach is needed”

“ If patients respond to the treatment within three months, they tend to respond over the long term”

Molly Shoichet

ofer levi

Robin Green

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The idea of a higher force — the spirits of aboriginal peoples, the gods of the

Romans, or the supreme beings that modern religions worship — is uniquely human.

Today, we call this idea “religion.” And it has played a powerful role in human history

since our species evolved from apes.

Our other major innovations — such as the use of fire, the invention of the wheel,

language, music, literature, cooking, understanding of the scientific forces that gov-

ern our existence — have an obvious, tangible purpose.

But why religion?

Marsha Hewitt doesn’t claim to have an answer. In fact, she says, no one definitely

knows why humans developed religion. She is, however, fascinated by the cognitive

ability — or to put it in more blunt terminology, the brain power — of humans to

imagine a force or forces beyond what we can see and touch here on Planet Earth.

“What we call religion is hard to define and there’s a great amount of debate,

even confusion, over a definition,” says Hewitt, a professor in the Department for the

Study of Religion and in the Faculty of Divinity at Trinity College. “I work with the

definition that it involves belief in superhuman or supernatural agencies that impact

our life and that we, in turn, can impact through certain kinds of rituals.”

Hewitt is also a practising psychoanalyst, helping patients deal with their lives

and life situations and how the unconscious influences behaviour.

“Our brains give us the capacity for symbolic thought. My particular interest is in

what are the cognitive and affective mechanisms that enable people to imagine and

believe in these counterintuitive beings.”

While she notes that although the reasons humans seemed to need religion are

hazy, there is evidence of us reaching out to a spiritual world from our earliest times.

“The first kind of evidence we have is seen in the evidence of burials. What has been

found appears to have been ritualistic or carried out at least in an organized way. But

what does it mean?”

She points to South African scholar David Lewis Williams, who has explored the

meaning behind Paleolithic art on the walls of deep caves, such as the Chauvet caves

in France featured in Werner Herzog’s Cave of Forgotten Dreams. “Williams looks at

ancient cave paintings and wonders what motivated people to go into the caves. He

believes the spiritual focus of the art is neurologically based, the images generated

from within their minds. But the people who made that art put themselves at great

risk to venture that far underground. They didn’t take this risk just to make pretty pic-

tures. There must have been a ritualistic meaning, the walls of the caves representing

a membrane between this world and the spirit world.”

Hewitt’s own research into the motivation for religion is currently focussed on

Sigmund Freud, the founder of psychoanalysis. She is working on a book on Freud

and religion.

“There’s a lot of misunderstanding about Freud’s critique of religion. Many people feel

Freud was just an atheist and had nothing but contempt for religion. That’s really not true.”

She says Freud anticipated attachment theory, which is now considered relevant

in evolutionary psychology. “Think of the infant who calls out to the world for sur-

vival — ‘Feed me, comfort me, help me to survive.’ That attachment system is an evo-

lutionary endowment that helps in the survival of the species. When we are adults it

quiets down, but it may become activated when we experience severe stress. Freud

says that in certain people, maybe those who didn’t resolve conflicts of early infancy,

the anxiety that is part of living may be so unbearable they have to find external

sources of comfort. So he wondered if religion is a product of the human response to

feelings of helplessness, vulnerability or terror.”

“In the beginning…”Marsha Hewitt explores the roots of religion – and the psychology that drives our need for a spiritual connection by Paul Fraumeni

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who are you? A funny person who loses her temper easily? A hard-working late-

bloomer who tends to run late? Or maybe you have a deeper sense of self beneath

these kinds of traits.

Evan Thompson wants to know how you know.

As a philosopher of the mind, he grapples with some of the

oldest and most enduring questions around: What is the mind?

What is the relationship between the mind and the world?

Thanks in no small part to advances in brain imaging technology,

these timeless questions are being examined anew with insights

from such seemingly disparate fields as neuroscience, psychol-

ogy and linguistics.

Thompson’s particular interest is the self. “What is the self?”

he asks. “What are the different ways we experience being a self?”

One sense of self we have is autobiographical. “We have a

sense of our life as a storyline. We project ourselves back into

the past though memory and into the future. This sense of self is

very much bound up with personality traits we attribute to our-

selves: I’m confident, I’m easygoing, I’m anxious.”

Another completely different sense of self is our awareness of being in our bodies

in the present moment.

Thompson collaborates with neuroscientists who use the minds of medita-

tors to help illuminate the self. If you or I tried to meditate, we would likely find our

minds wandering, typically because our autobiographical sense of self kicks in. We

mentally compose our grocery list for later, or replay conversations from earlier in the

day. Skilled meditators can turn off this autobiographical sense of self and shift into

the embodied sense of self. Switching between these two senses of self while hav-

ing their brains imaged can show researchers which parts of the brain govern which

senses of self.

For his part, Thompson wants to understand our overall sense of self.

A book due out in 2013 will explore how sense of self changes across

different states of consciousness like daydreaming, being attentive,

sleeping, dreaming and different kinds of meditation.

“There’s never been a better time to be a philosopher of the mind,”

says Thompson. As a member of the Mind and Life Institute, he works

with researchers studying the minds of Tibetan monks as they meditate,

and believes that as much as philosophy benefits from advances in neu-

rosciences, it also contributes a great deal in return. In the case of stud-

ies of meditation, for example, “Neuroscientists need people who know

the philosophical tradition of the meditators and theoretical underpin-

nings of the practices that come from that tradition.”

In other words, it’s not just about the brain.

“Saying that you can understand the mind in terms of the brain is like saying you

can understand a Gothic cathedral in terms of the stones that make it up,” he says.

“Stones are crucial, but so is architecture, iconographic traditions, the overall environ-

ment—that’s what makes it a Gothic cathedral.

“Our identity as persons isn’t just a matter of the brain.”

“In the beginning…”Marsha Hewitt explores the roots of religion – and the psychology that drives our need for a spiritual connection by Paul Fraumeni

The mind versus the brainPhilosopher Evan Thompson brings new technology to old questions by Jenny Hall

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THE BRAIN ISSUE EMOTIONS AND MOODS

CamH’s Jeffrey meyer: “ultimately, we’d like to say, ‘Here are four things you should do to avoid depression.’ “

10 E D G E / W I N T E R 2 0 1 3

Depression is a disorder of many names. Winston Churchill, for example, called his

depressive episodes the “black dog.” Others, meanwhile, refer to the condition as the

blues or the blahs. Despite the colloquialisms for depression, the reality is the disease

can feel like a dark, endless tunnel — one that researcher Jeffrey Meyer hopes to pre-

vent people from entering.

Meyer, an MD/PhD and professor in the University of Toronto’s Departments

of Psychiatry, and Pharmacology and Toxicology, is head of neurochemical imaging

for the Mood and Anxiety Disorders program at the Centre for Addiction and

Mental Health (CAMH). Also the Canada Research Chair in Neurochemistry of Major

Depressive Disorder, Meyer is focused on answering this question: what is needed

to have a healthy brain?

To that end, Meyer wants to create specific recommendations to help people

sidestep major depressive disorder. Typically just called depression, the condition

is much more than a brief period of melancholy — it involves ongoing feelings of

deep despair.

“Ultimately, we would like to say, ‘Here are four things you should do to avoid

depression,’” Meyer says. “It would be similar to the strategies for avoiding heart

disease, which include eating right and exercising, but in the case of depression,

the strategies would be more complicated than simply saying ‘avoid stress.’”

That advice could have a significant impact on mental health worldwide. Indeed,

depression affects more than 350 million people globally, according to the World Health

Organization. While there are treatments for the condition, such as medicine, therapy and

lifestyle changes, they don’t seem to work for everyone. And at its worst, depression can

lead to suicide. In fact, one million people take their own lives each year around the world.

So what happens in depressed brains? Meyer is focused on monoamine oxidase A

(MAO-A), an enzyme that breaks down the chemical messengers serotonin, dopamine

and norepinephrine. When the brain is depleted of those mood-related substances,

people experience a sad emotional state. And those feelings, along with pessimism,

are harbingers of depression.

Although scientists long believed that a chemical imbalance in the brain caused

depression, in 2006 Meyer and his colleagues determined conclusively how that

process actually works. Using a brain imaging technique called positron emission

tomography, the researchers found that the level of MAO-A was considerably higher

in the brains of those with untreated depression. Meyer subsequently made other

landmark discoveries. For instance, he found that MAO-A is elevated in several high-

risk states for clinical depression, including prior to the condition’s recurrence, during

early withdrawal from heavy cigarette smoking and just after childbirth.

Today, Meyer is using that information to study and assist those with high MAO-A. For

example, he has developed a natural health product to help regulate the MAO-A of new

mothers with postpartum depression. After giving birth, a woman’s estrogen level drops

considerably, triggering a surge in MAO-A level. Meyer also aims to develop interventions

to adjust the MAO-A of people at increased risk of depressive symptoms, including pre-

menopausal women and those with substance addictions.

Finally, in the future, on top of designing preventive strategies to help the general

population avoid depression, Meyer hopes to bring peace of mind to those with the

treatment-resistant form of the disorder. That two-step process will involve identify-

ing subtypes of depression and determining which treatments best normalize brain

changes in each subtype.

Inside the depressed brainCan Jeffrey Meyer ease what Churchill called “the black dog?” by Dana Yates

U of T has long been an international leader in psychology research. In 1891 —

just as mental health giant Sigmund Freud was beginning to make his mark — the

university established North America’s 10th psychology lab, with a full-fledged

department founded in 1927.

The focus of U of T psychology in previous decades has been in “experimental”

research, exploring primarily the workings of the mind/brain from a multitude of per-

spectives, and producing notable advances in a number of areas — such as Endel

Tulving’s renowned discoveries in how human memory works. The Department of

Psychology at all three U of T campuses continues to offer outstanding undergraduate

and graduate training in experimental psychology but still does not offer a formal train-

ing program in clinical psychology.

Very soon, U of T will take a major step further when U of T

Scarborough (UTSC) launches a formal graduate program in clin-

ical psychology.

“I’m excited that the University of Toronto’s Department of

Psychology has decided to develop a formal graduate program

in clinical psychology, which has been the aspiration of many in

the department for years,” says UTSC professor Michael Bagby,

who is also a senior scientist at the Centre for Addiction and

Mental Health (CAMH) and the Campbell Family Mental Health

Research Institute. Bagby joined UTSC in 2011 and has been

instrumental in designing the new program.

Collaborating with Bagby in the proposed UTSC clinical pro-

gram are psychology professors Anthony Ruocco, Marc Fournier,

Amanda Uliaszek, and Konstantine Zakzanis. There is a search

underway for two more clinical faculty — one at the rank of full

professor and the other a clinical lecturer — and these new fac-

ulty hires are expected to join the existing clinical faculty in July

2013, bringing the full complement to seven full-time clinical fac-

ulty. In addition to this complement, nearly 20 other U of T fac-

ulty, most of whom have their primary university appointments in

the Department of Psychiatry and/or academic hospitals, will be

cross-appointed to the UTSC clinical program. Although the pro-

gram will be housed at UTSC, clinical faculty (and students) from

all three campuses will participate.

Bagby explains that while experimental and clinical psychol-

ogy streams both involve research, the key difference with the

clinical side is that it also is focussed on the provision of care to

those with mental disorders and on identifying the causes of

these conditions.

“The image that comes to many people’s minds is of a patient

receiving psychotherapy in a clinical psychologist’s office. That is

a common part of clinical psychology, but it’s much more than that. The faculty mem-

bers in the clinical psychology program train clinicians who are also scientists. We use

the body of scientific literature examining mental disorders to inform our models of

treatment and assessment. ”

The program will be relatively small and highly selective, admitting no more than

eight students in its first year. “It will grow in future years, but we will need to keep the

program small so as to provide intensive instruction in both research methods and the

development of clinical skills, including psychotherapy training and the diagnosis and

assessment of mental disorders. Toward the end of their graduate training, students will

also be required to complete a year-long internship, typically in a hospital setting.”

Says Ruocco: “It is an intensive undertaking because you have to be not just an

excellent researcher but also an excellent clinician. It’s rewarding in the sense that

research is informing your care, with the ultimate goal of alleviating the psychological

pain of those suffering with mental disorders.”

Training in psychotherapy, for example, requires significant time and work. “Most

people think that a psychologist just closes the door and talks with the patient,” says

Bagby. “But scientifically informed psychotherapies are typically highly structured. There

are many different types of psychotherapeutic interventions. For example, empirically

supported psychotherapies such as interpersonal psychotherapy and cognitive behav-

iour therapy are highly effective in the treatment of major depression.”

“Similarly,” says Ruocco, “dialectical behaviour therapy, which is also an empirically

supported psychotherapy, is highly effective in treating those with borderline person-

ality disorder. All of these evidence-based psychotherapies require significant training,

and a high level of expertise is needed to implement them effectively.”

Ruocco notes that the launch of the program is timely given the need for psychologists.

“Ontario, per capita, has the smallest number of licensed psychologists in Canada. This

is at a time when people are experiencing significant stress and many of those suffering

from mental disorders are currently not treated. That’s why it is so important for U of T to

develop this program. U of T is particularly well positioned to embark on such an initia-

tive given its association with our nine partner hospitals, which provide opportunities for

‘hands-on’ clinical and research training to supplement classroom instruction.”

Bagby sees the launch of the clinical psychology program as “the essence of what

a comprehensive research university can do — provide top-notch education and

intensive research training in an area that makes a tangible impact on the health of

Canadians. We’re eager to get started on this program.”

U of T Psychology enters a new eraUTSC readying to launch graduate training in clinical psychology by Paul Fraumeni

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Donald Stuss is a professor of psychology and medicine at the University of Toronto,

where he holds the title University Professor — the highest honour U of T bestows

on its faculty — and a senior scientist at Baycrest’s Rotman Research Institute.

A pioneer in the study of the frontal lobe, he’s recently taken the helm of the newly-

formed Ontario Brain Institute (OBI), where he serves as president and scientific

director. Here, he’s tasked with coordinating and accelerating brain discovery

and innovation in Ontario, which is home to more brain scientists than any other

jurisdiction in Canada.

why is research into the brain important?

The brain is everything. It’s important for two major reasons. First, if you want to

optimize people’s quality of life, it will come primarily through the quality of their

brain function. That’s true whether they’re healthy or have disorders. Second, there

is no greater cost to society, both direct and indirect, than the cost that’s incurred

by brain disorders.

why is the creation of the oBi important?

The OBI is integrating basic research into care, and patient advocacy groups

into research, so research discovery will have much more rapid impact on

patients. OBI will bring industry to the table to accelerate cures and discovery. And

because it works across institutions, it will maximize the impact of research.

I’ll give you an example. Say researchers are going to look at the genetics

of Alzheimer’s disease. They used to study a group of 100 or 200 patients. Now

researchers are publishing studies looking at 8,000. If Ontario wants to be a

leader, it has to increase the number of patients in its studies. OBI can help with

that by having researchers and clinicians work together.

what are your goals?

In this initial stage of development of OBI, we are starting with three diseases:

cerebral palsy, epilepsy and neurodevelopmental disorders. That last one is a

category that includes autism, attention deficit disorder, obsessive compulsive

disorder and intellectual disability. It will be important to extend these programs

to other brain disorders, both neurological and psychiatric.

The idea is that a disease is not just a single thing. What is the relationship

between autism and attention deficit disorder, for example? There are relationships

between them — some are behavioural, some are genetic. We are setting up the sys-

tem so we can actually start to look at the relationships across diseases. This system

will also enable us to study how the underlying mechanisms influence the initiation

and progression of disease.

The integrative nature of the data is key. The comprehensiveness of our data will

provide the power to understand these relationships. And it may be that a cure or a

treatment will be found for five per cent of the population, but you would never find

it without having tested the entire population to find that five per cent.

So is the goal a cure for some percentage of the population?

Goal number one is treatment — improving the quality of life for individuals and

families. But if you set up the discovery system properly so you’re studying the mech-

anisms of disease, you can potentially also look for something that stops the devel-

opment of the disease — or significantly slows its progression. The OBI is getting

people to work together across the province, across disciplines, across institutions.

We’re combining data. We’ll be able to ask things in the future that we don’t know to

ask now. Because we’ve set the data up properly, we’ll actually be able to go back to

it in the future. And as our understanding of diseases unfolds, people will be able to

ask more and better questions.

How much do we understand about the brain right now?

A lot more than we did a long time ago. But do we know enough? No. We need

to know a lot more about the brain itself — and then apply that knowledge to more

fully understand brain disorders.

“The brain is everything” Five questions for Donald Stuss, president and scientific director of the Ontario Brain Institute by Jenny Hall

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