and so I'm now going to show you
the most important slide I ever
can put in a talk
and it's actually unnerving
because
I don't care how many people I put on
this acknowledgement slide
I can look out there and see about a
hundred people I probably should have
acknowledged in terms of
informing our research and the work I'll
talk about today
but I'm gonna be shameless
opportunistic
and in the next hopefully less than twenty minutes I will
present as much of my fellow's work in a
hopefully a cohesive way really focusing on
how changes in development can impact self-control
and considering that as a context itself
we all know that
the adolescent brain and adolescent
behavior has received a lot of
attention from the media I tend to refer
to it as the media
media darling and it's because we can really
voyeuristically just open up that
head and look
at while the teenager's behaving and
doing what they're doing and seeing how
the brain activity is changing
during that time now too often the way
that we describe this period as
if it is a brain that has no brakes no
steering wheel
and only an accelerator and that's suggesting almost as if there's a hole
in the head but when you open it up and
look in
it looks pretty close to an adult's brain
so what's important for us to try to understand
is how this typical and
I'm gonna suggest necessary stage of
development
how there are changes in the brain that
allow it to meet
the many different challenges of the
adolescent period
from physical cognitive sexual and social
and we usually talk about this period
as beginning right around the onset of
puberty
but when we
talk about the end if the definition
of adolescences
is the transition from being
dependent on a parent to relative independence
many of us have discussed how our
children may be in that period for a
long long time financially
but over the past decade
and trying to really look at brain and
behavior correlations and associations
we've been able to characterize the teenager
as an individual who is incredibly sensitive
to rewards also sensitive to threats
social influences and we think
it's a combination of these things
that impact their degree of impulse or
self-control
and their risk-taking behavior there have been
least three nuerobiological models
that have been put
out there to try to explain the adolescent brain
one of the first that Larry Steinberg
talks a whole lot about
and his work is the dual model system
this suggests orthogonal
hot/cold systems that presumably map
onto a limbic system
and a prefrontal region and it's more
value based
and then there is it's a lovely
heuristic when you're talking to
the media or you're trying to change
policy
and then there's an elegant model
where Monique Ernst and colleagues
sorta tried to separate out
aspects of that limbic system according
to balance
linking positive and negative balance
to the accumbens
and the amygdala respectively and
then we built on that work
and actually in the mid 2000's came up
with
a model that we think is more circuit
based
largely based on work by Adriana
Galvan at that time
looking at specific circuits and how
regions within those circuits had
differential patterns
of development and that's the imbalance
model
Sarah-Jayne Blakemore has recently published
a paper where she talked more about
a mismatch
in development of regions such as the
amygdala and the accumbens to
the prefrontal cortext
this is an interesting perspective
to try to get away from an imbalance that
I think some people think has a negative
tone to it
I don't particularly I'll try to unpack
that but this is just talking about bium
differences and there's no room for the
circuit or the connections
to really change here so let me just
show you this little
video where
what we know from the non-human animal
and human work is that
there are a number of systematic changes
in the limbic system particularly
subcortical systems
where you get strong local connections
you see peaks in
neuro chemicals like dopamine and neurotrophins and cannabinoids as well
and you see that occurring before you see
it in the screen area
in the prefrontal cortex and so what
our balance model suggests is
during adolescences with this
regional development
you get this sort of imbalance
when you're in the heat of the moment
where the limbic systems tend to win
out and so it's not that
the amygdala and the accumbens can't
call or signal the prefrontal cortex
it's just that that system and the
distal projections
are not fully mature so really all these regions
if you're getting a projection in these
subcortical systems
they're still developing they're still
forming those connections
and this is different from adults
because
the circuitry is mature and it's all so
different and this was what was so
wonderful about
Adriana's work not only did she show
differences from adolescences to adults
which I'll
show you in a moment but also how
these effects are adolescent
specific and are not seen in children
as well which we think is because immaturity
in ascending as well as the descending
projections
and in simplistic ways we've talked
about this building on John Cohen's
sorta idea of the prefrontal cortex as
balkanization of the brain
and we talk about the imbalance of being
on the Starship Enterprise
and you've got mister Spock who is
logical
and you have Captain Kirk who is
someone who has passion and he can
show range
and sometimes he flies by the seat of his
pants and when he does that
if they're on the bridge of the Starship
Enterprise that's when Spock is needed
so what I'm suggesting to you is it would make
sense during this period of development
that you would want regions to call a
system that's going to help you
regulate so that you no longer need
your parent to be in your self
regulation and you can do it
on your on this is very similar to
learning
data of Earl Miller and many others
where they've shown changes in
subcortical systems
before prefrontal so we're just
suggesting it's more protracted period
during development so how do I define
self-control in the context of the
symposium well
self-control is
really our ability to suppress
maladaptive thoughts actions desires
and emotions in favor of
adaptive ones and if we go back to
how adolescence is characterized and the
most recent work
really we're talking about aspects of self-control
and two different descriptions come
up of the adolescent
multiple times as if they're synonymous they're impulsive
and they're risk taking and I wanna unpack that for you little bit because really they're
different developmental trajectories
for risky behavior and impulsivity
and a slightly different overlapping
neural circuitry
the way we measure and impassivity in
the laboratory we can use an anti sig cog test
to stop signal
we like to use a go nogo task or whak the mole
task at this point since you want a
cocktail I'm not gonna have you proceed
in this task but basically all these
tasks do is they build up this habitual prepotent response
by having many targets that you're
pressing to in this case the sneaky
mole that keeps popping up in your garden
that you don't want there so you whack it
I will tell you in a psychiatry department it was nice to get them
to say instead of whack
yes I started hearing yes yes yes every time
the mole popped up and people are trying
to come in to see what
the excitement and enthusiasm was about
in the psychiatry department
so what you don't want to do is mash a vegetable and so basically
the mole can be tricky you want to press him
and you want to press to him
but you don't wanna press to the eggplant
so if I had each one of you perform this
task you would see
that there would be individual
variability in your performance I know some of you
might be a little bit lower and then
if we looked across
development what you see is this
ability is really emerging
right around the late adolescent years
teenage years up but if we put these in neat little bar graphs
like we tend you wouldn't see this
variability and you would basically see
sort of a montonic decrease in the number of times you
whacked the mole when it was actually a
vegetable and you should not have
now we know from TMS studies and
lesion studies in nonhuman primates
that there are certain areas of the brain
that make it more difficult for us to
engage in impulse control
and when you perform these tasks in the scanner
and you look at the pattern of brain activity
you basically see a region in the
ventrolateral prefrontal cortex and
the activity in this region when you're
correctly
able to engage in impulse control
correlates
with the actual performance and we
see across development
that there's this monotonic decrease
with age from childhood
to adulthood notice children are activating
this region more
for the correct trials and
they're actually the same ones who are
having the most difficulty on the task
if you just look at their overall
performance
and the signal but there is nothing 
adolecent specific
in these data it's just continuing to
decline in terms of the amount of
activity and the number
errors so now I just want to move to some of the work that brings in
reward value incentives and how that
drives our behavior
and this is really again focusing on the
elegant work of Adriana Galvan
who when she was doing her thesis she
got tired of people saying adolescents do
what they do because of the prefrontal
cortex and so
she wanted to try to look at reward
circuitry
and decided to use a paradigm that work
from schultz
was using with his non-human primates when he
looked at dopaminergic
firing to those rewards and she used
couple paradigms the one I'm going to talk about today
is one in which you simply had three
discrete stimuli
these are pirates and unbeknownst to the
subject
you mapped reward for those cues
on to different amounts of money now
the task they had to do was simply say
what side of the screen the pirate was on which is
pretty easy to do
so even children can perform this at 95
percent accuracy
but what she saw in their performance
even without
the subjects being able to articulate
this that when they saw a cue
that later predicted a larger reward
reaction times got slower and slower and
even though they weren't getting a single coin
when they pressed to this cue they got
significantly
slower it's indeed relative now
in this task when you place it in the
scanner and you look at the pattern of activity
you know the question is what maps
onto these differences in latencies
and not surprising to us
is that reward circuitry envolving
the Orbitofrontal Cortex and the accumbens are showing monotonic increases
as you increase the amount of reward
the individual gets from small
medium to large and you see that in the
orbitofrontal cortex too
but Adriana wanted to know how does this
change across development cause at this
point people had shown differences
between adolescents and adults
but we really didn't know what was going
on with children
in this orbital frontal region
what we see is there's a decline in
activity when you perform tasks like this
as a function of  age group but the
striking differences
were in the accumbens an area that's very
important about
learning about outcomes too and those
an exaggerated response in this
region now why is this relevant to
adolescents and their behavior because
the activity
to a reward is actually
correlated with the amount of likelihood
of engaging in risk-taking
so activity to receive a rewards
was then correlated with their
self-reports
of this risky tendencies and we also
know that when adults are about to make
a risky decision we see elevation in
this region
as well so these were the data that led us to develop
the imbalance model and it was basically showing accumbens
is beginning asymptote
before the prefrontal cortex
it's also the case that social influences
can impact us and I wanna go back
and sort of link social influences
just simple cues later Strindberg showed
just having a peer next to you can lead to
you engaging in risky behavior but I
want to highlight work by
Leah Somerville who was a
postdoctoral fellow at the Sackler Institute
and basically what Leah did was she
examined the patterns of behavior and brain activity
when instead of having a mole that
you were
whacking and trying to refrain from
whacking the
the produce that was appearing out of the ground
she used smiling social cues smiling
faces that were developed by NimStim
Nim Tottenham who developed NimStim
another fellow from the Sackler Institute
told you I was going to get all these guys in
and so what she showed is when
you ask adolescents not to press to
a smiling face
relative to a neutral one that they
can't stop themselves
they have a really difficult time not
approaching
that positive cue and you're not seeing
that pattern
in children or adults and if you look
at the neural correlate of that
it's the same region that we see is elevated
in the teen when they are receiving
a large reward so
what I cannot do it have a talk
about self-control
and not highlight my work with Walter Michelle
so hold this in mind and I wanna
talk about individual differences
and then I'll bring it right back to
that and that is with Walter
we had this wonderful opportunity to
look at his original cohort of
children who had played the delay
gratification game
or Marshmallow task when they were four
and we brought them back when they were forty
we actually scanned them at Stanford in collaboration with Ian Gotlib
and the question that we had is are low delayers and high delayers
are the low delayers simply
impulsive
and so we can use tasks like the
whack-a-mole to examine that
but what we did is we tested these
individuals in their mid-forties and
we broke them out into
those individuals who over the years
looked like they were consistently
low and others who looked like they're pretty
consistently high delayers
and we have them perform
the impulse control task where they had
to stop and not press to a neutral expression
versus having to stop themselves and not press to a smiling face
we use these social cues because marshmallows just don't do it for us when we're in our forties
there are other things that we are
very social beings
so the the results for
just the the neutral or kinda hold version
of the go nogo task showed no
differences between these groups
but the minute you have this appetitive
social positive cue
those forty-year-olds who couldn't wait to get two marmallows
in their mid-forties they're having
trouble waiting
and stopping themselves when they see
something pulling their
attention something that was alluded to
earlier
and if you look at the neural correlates
of this overall across a task when
you're performing a no-go trials
it's the case that low delayers are not
activating this region
in the prefrontal cortex as much as a
high delayers
but the area that really
discriminates
them based on when their
performance is really faltering on
this hot trials again
looking down on top of the brain this is
the actual image now
it's in this area in the nucleus accumbents
so just to summarizes those findings for you
there are developmental and individual
differences in self-control
where adolescents show a heightened pull
to these positive social cues
and so do low delayers
and the neural circuitry
is very similar across these the
last
I'm few minutes I just wanna talk about
threats as well
and this is work by Michael Dreyfus an
MD PhD student
reanalyzing data from Todd Hare's thesis he's now at Zurich
and basically all this is is examining
how adolescents respond when you don't
have a smiling face but now you have a
threat cue
that is I don't think that this fearful
face is scaring you right now
but we have learned over a lifetime that
something bad or there's some
uncertainty in what's going on around
us and so we orient
to these as if there is
potential danger and using the same task
and using these cues
we were surprised to see that teenagers
look like they're drawn to danger that
is they reacted to these
cues relative to neutral so we always
have a control baseline
and you don't see this pattern in children or adults at all
now we know from Todd Hare's earlier
work that when you see these cues
that structure that was talking about
earlier the accumbens
I mean the amygdala is actually
heightened
in activity in adolescents when they're
presented with these cues
and so that comes back to the circuitry
that we talked about
at the beginning of the task no longer
are we talking about valence specific
behavior right because we have positive
and negative cues but we're talking about an action-based
how you're approaching that information
and
so part of what I did unpack in the
circuitry is that yes there's signals to the
prefrontal cortex but there's this
really interesting circuit that's
a projection from the amygdala to the accombeds that
has show with optic genetics that if
you activate it
it leads to approach behavior and so
with these local connections that we're
suggesting are forming during
adolescents
then what you get is more action
driven responses
when the system is activated and you
don't have the prefrontal cortex
projections to inhibitory cells there
to sort of block that affect Aaron
Heller
who just left the Sackler Institute for the University of
Miami wanted to test this so he looked at
connectivity patterns based on the
a whole host of subjects you'd run on
the emotional go no go across age
and he wanted to see if the street that
the connection between the amygdala and the accombeds
was actually related to errors and
what he showed is
the stronger the connectivity between
these regions
the more false alarms that you get but
what was also interesting to bring it
back to the prefrontal cortex so we can
look at this little component
I really simplifying the circuitry
tonight is that
the ventral prefrontal cortex actually
modulates this
so that the stronger the projection
from the prefrontal cortex
to the amygdala the fewer false alarms
that you're making
and that did not hold when we looked at
the prefrontal cortex
to the accumbeds so these results suggest
that
adolescents are impulsive regardless of
the valence
of the cues during this time when
we look at simple impulsivity tasks in
the heat of the moment we think that's
driven by
changes in the circuit locally before
more distal
prefrontal systems can actually
project to
modulate those systems and
I just wanna end this last minute and
say that if it is the case
that a region a subcortical regions
still
receiving prefrontal projections than
basically what we're saying is that's
protracted development
of that circuitry and so Ali Cohen
has been trying to understand
when does the capacity for self control
and regulation mature
because you're in New York State a place
where age of majority is eighteen
but you can charge and actually try
a sixteen or seventeen-year-old as an adult
and there's also a lot of policies across
the United States in terms of whether or
not you're eighteen of twenty-one
in which you're deemed an adult and so
she has been using the same two tasks that
I described
and her basic question is does an eighteen to twenty-one-year old look more like an adult
on these tasks or look more like a teenager
and what she's shown is that
eighteen to twenty-one-year-olds do not differ from
younger teenagers but they do differ
from older adults likewise
if it's a threat cue or if it's a
smiling face so these are things that we
need to consider and are very relevant for
policy
so on that I'd just to end and say
adolescence is usually described as this
roller coaster ride of a lot of thrills
but actually there are thrills and fears
and it's important for those
to have the opportunity to occur so that
they can actually help rewire
the system to help regulate these systems
for
moving forward and being able to engage
in adaptive behavior
that's necessary in adulthood so thank
you for your attention and for waiting this long
