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>>ARMIN RAZNAHAN, M.D., Ph.D.: Does the brain scale-up like Photoshop? Just like a linear expansion? Or is it a case that in larger brains some
regions become notably large and others fail to get as they should, essentially. So what you see here is a spinning human brain,
with a map that ansers that question. Where you see red, those regions expand prominently,
as a function of brain size. in contrast, where you see blue, these regions
expand, but not as much as the red regions. They become more expanded than the blue regions
in larger brained individuals. This does not enable a large brained person
to say “My brain is better then a small brain person.” So our question is about bigger individuals
compared to smaller individuals. The two other routes to a big primate brain
are evolving one — i.e. the difference between humans and non-human primates. Or growing one. The difference between adult brain size and
the size of a child’s. This map that we found very strongy aligns
with both of those maps. And what this is telling us is we seem to
detecting some sort of blueprint — an architectural blueprint, if you like — with the primate
brain, given that all three routes to a bigger brain induce this sort of shift in brain organization. Which was really very striking for us and
suggests that its a sort of deeply ingrained biological signature. So one metaphor is: If you think about making
a garden shed as big as the white house, you can’t build it the same way. It has to be differently proportioned to be
able to stand up. And it seems somehow that bigger primate brains
need to construct themselves a different way to operate, relative to smaller primate brains. What was prominent for these red regions,
is that they seem to bear functional and cellular signatures of integration. They specialize in combining information from
lower order systems within the brain. In contrast, these blue regions that don’t
expand as much tend to be involved in what are called lower order sensory motor tasks. Basic vision, sensation, motion. So genes that were involved in the long processes
of neurons that are important for connecting with other neurons, are particularly highly
expressed in these red regions. These red regions have high levels of expression
of genes that have to do with mitochondria, that have to do with energy consumption and
generation. So a hint that these regions might be potentially
expensive, requiring more energy than the blue regions. At rest, we found that these red regions consume
a lot more energy than the blue regions do. So altogether, this seems to suggest that
there’s a very basic architectural plan by which having a larger primate brain consistently
seems to require making some parts that are important for integration and hungry for energy,
disproportionately, or more notably large in bigger brains. The brain is spending its money differently. If you know that brain shape changes as a
function of brain size, it’s going to help us more accurately detect smaller sub regions
of brain differ as a function of age, between males and females, potentially between patients
and controls, patients and typically-developing individuals. All of these things are associated with brain
size differences. It’s a signal biological investment. These red regions have another signature in
that they seem to be consistently impacted by a whole range of neurodevelopmental disorders. So they may actually be a kind of important
key to understanding how a whole range of gene and environmental changes can impact
higher mental functions. Planning, processing difficult tasks in humans. That larger brains are kind of constructed
more differently than smaller brains. And that different construction presumably
is there to perfectly suit each brain size. So evolution doesn’t sort of spend its money
unwisely. So we’re not suggesting that having larger
areas in these red regions smaller area in these blue regions is necessarily good. But they are a clue about how the brain is
having to optimize its configuration at different sizes. And that give us some insight into how the
brain is operating. So we already know from prior work that within
humans, there’s a subtle relationship between general cognitive ability, or IQ, and brain
size — such that there’s an association that larger brained individuals, on average, tend
to have a slightly higher IQ than smaller brained individuals. To the extent that there are functional differences
between large brains and small brains — and that’s not something our study directly addresses
— what our study shows is that there are also consistent organizational changes between
large brains and small brains. And that knowledge that observing that the
brain needs to consistently configure itself differently as a function of its size is an
important clue into the how the brain functions in health. And it’s potentially a clue into how the brain
has difficulties in disease states. What is clear from our findings is that the
red vs. blue regions seem to have a different biological cost, from a number of perspectives. One, it costs money to grow tissue. And the core of our finding is that the red
regions grow more than the blue regions as a function of increasing total brain size. So there’s biological money being spent to
build that extra tissue. The second signature of cost comes from direct
measures of energy consumption at rest. And at rest, we know that these red regions
seem to be a bit greedier — to receive more oxygenated blood than the blue regions. And we interpret that as making the assumption
that nature spends its money very wisely. That there must be a kind of functional reason
for that differential investment. This is one of the most comprehensive maps
detailing how the brain spends its money. It gives us leads regarding which brain regions
we need to focus on and how we need to study them. And that’s real advantage, because the brain’s
a big place and there are lots of questions you could ask. And having leads like this to help you know
where to dig is a very, sort of, powerful, potentially powerful, step. For us, because we study patients that often
have alterations in their total brain size, by having these maps, we can do a better job
of pinpointing which sub regions of the brain seem to be disproportionately altered in those
patients. And that is important, because if we can understand
the map of altered brain organization in patients, that might being us one step forward, ultimately,
in the future, to potentially helping them. [Music]

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