Januari 02, 2017
(beeps) (light upbeat music) - i wanted to sort of pitchor present the work today in the context of the effects of stress because of the highburden that mental illness has on young people. that is as many as 40%of young people today experience a mental illness. the majority of these arerelated to anxiety and stress.
and if we don't treatthese early, they can go on to lead to chronicillness, both psychiatric as well as physical illness. so the questions that we've been asking in our laboratory over the years is how are these early life experiences impacting emotionalwell-being and the underlying brain circuitry involvedin that well-being? and ultimately, what we need to do is
to use this informationso that we can facilitate and enhance healthy brain development and also, of course,well-being of young people, which is then gonna bewell-being of our society. but if we first takejust a simplistic look at all the changes that are happening in post-natal development,what you'll see is that there is dramatic changes just in the number ofsynapses throughout the brain
that develop regionally. so we see a proliferationand a subsequent pruning of these connections. simultaneously, theirchanges in nerve chemicals and neurotrophins thatare absolutely essential to development and learning. and with all these regionalchanges, it is co-occurring with increased myelinationthroughout the brain, which is making the connections stronger.
so we've been focused onall these dynamic changes and trying to understandwith just one picture using human imaging andfocusing on one circuitry that's really important for our ability to process emotional information. so emotion regulatory andemotional reactive processes. and during this time, duringchildhood and adolescence there are major changes in this circuitry, and we think that theywill, are one pathway
for us to seeing howearly life experiences are reflected in them and howthis continued development may also be a windowof plasticity of sorts where we may have the biggest change. now, in human studies, one of the ways that we try to look atthis, at these circuitries in the behaving humanbrain non-invasively, is to use simple stimulatorcues that we present. so here are, here's an example of a cue
with emotional information. we examine how these cuesimpact both brain and behavior. these cues can be positive, smiling faces, or negative, or they can be neutral. but what we see is even if you are in the laboratory performing this task, if we ask you just to press a button whenever you saw one of these cues, you would be significantlylonger in detecting
a threat cue, a fearfulcue, than you would be to a neutral or happy as you see here. so we have a longer latency there. it's adaptive when we see cues that have some uncertainty or ambiguity. i don't think for a minutewhen i present this cue to you that you are threatened by that. however, we learn over a lifetimewhen we see cues like this that there might be potential danger,
and what's very importantfor us to understand is in this context, is it a threat? so if a bear were to come into the room, i might have an emotional response. but the circuitry isimportant if i saw a bear in a zoo to know that thatbear, in that situation, i would be safe because theywere behind a cage or wire. so now, if we look at these responses in this change in our responsesdepending on the potential
threat of information in our environment, if we open up the brain and look inside, the areas that tend tobe related to that delay in our approach behaviorin such situations involve the amygdala andthe prefrontal cortex. and hopefully, what younote from this slide is that the amygdala,the more active it is, the slower you are to respond. the amygdala is veryimportant in picking up
the emotional significance ofinformation in the environment and has been associatedwith emotional reactivity. in contrast, the prefrontal cortex, which has direct projectionsto the amygdala based on elegant animal work andmore recent human work, that area is less active whenyou're really slow to respond. and the more active itis the quicker you are. that is, you see a potential threat. you are able to understandin this particular situation
with repeated presentations of it. get over yourself. alright, already. nothing's gonna happen to you. now, i've just made a sortof claim that over time, nothing's gonna happen to you. well, let's look at that in the brain and what systems areabsolutely essential for that. what's important when we look at
with those repeated presentations how well you habituate to these cues is this inverse couplingbetween the prefrontal cortex and the amygdala in this circuitry. and this inverse couplingor negative connectivity seems to be changing radically from childhood to adolescence. and it is when you are notable to habituate that response that is associated withheightened anxieties,
so i just want you to focuson this quadrant for a moment. and basically, if youlook over at the y axis, that's amygdala habituation,and it's a negative score. that means not only was therenot a change in how active the amygdala was to thesecues but that it was actually sensitized and it wasincreasing over the course of the experiment. and that's related to the highest level of self-reported trait anxiety.
now, some of thesepictures had a lot of data, and i think data slides and pictures are worth 100 or 1,000 words, but movies might tell a simpler story. so this is an example ofan individual who reports low anxiety, and they're being presented with these cues of potential threat. so you'll see, there's bilateral activity in the amygdala withrepeated presentations,
but then, it's like thesystem begins to return to baseline, and it turns blue. that represents from the increase going back down to baseline. in contrast, when we look at an individual with high anxiety, webasically see a similar pattern at first with this bilateralactivation of the amygdala, but then, it stays up andit stays up and it stays up. and it doesn't return to baseline.
so it's that vigilant stateof that anticipation of threat and an uncertainty of whatthese cues potentially mean. so, two different pathsthat we have taken in trying to understand these two verydifferent neurosignatures here is to look at differencesin genetic factors that may explain this, but in the interest of the symposium today,also, in the environment or experiences that we have. so how does early life stress impact
the development of the circuitry? and we have used really an extreme example of early life stress. it is an unfortunate buta natural occurring one. and that is children whogrow up in the orphanage. now, in the orphanage experience,all the orphanages vary. but there's always gonna besome fragmented caregiving because of the highratio of so many children to a single caregiver.
so what we've been interested in is as these children are adopted to families in the united states, we'vebeen trying to understand how this disregulation oftheir needs not being met, how there's not attunementin the child's needs with what a caregiver canactually provide to them, how that impacts theirability to regulate self. but particularly today, i'll talk about how to regulate emotion.
so again, we use these simple cues, and we ask children who have been adopted from the orphanages aswell as a comparison group who have not been adopted,who live in the united states. they all have moved. the adopted children have beenhere for at least two years to make sure they get acclimated to their new home and theirnew culture and environment. and what we do is we presentthese cues of potential threat.
but in the task we tell'em, you know, ignore these. try not to pay attention to them. and you find, in thesituations in which you have these cues relative to situations where you present a smiling face, that the adopted children are much slower in anticipation of one of them occurring. so even if it's a neutralface on the screen, if they know they're aboutto see a threatening face,
they're really hesitant to respond. but if it's to a happyface or a smiling face, you don't see a differencebetween the two groups. now, this is paralleled in the brain by enhanced activity in the amygdala. and that's shown here onthe left and the right side. but what i think is importantabout these findings if first, this is greateractivity in the children who were adopted from orphanages abroad
relative to the comparison group. the area in blue is actually more active in the comparison group. this is a part of thebrain that's important for attention regulationand emotion regulation. so one is being able to regulatetheir emotions and ignore. and the other is quitereactive, that group. but more importantly, whenyou see images like this, and you have these neurosignatures,
it is how does that relateto their actual behavior when you get them outsideof the scanner environment or the laboratory. and so, we measured how the behavior between caregivers andtheir adopted children when they had been separated briefly and then, they were reunited. and we looked at the amount of eye contact they had with their caregiverwhen they were reunited.
and basically, we see that themore active the amygdala was the less eye contact theyhad with the caregiver. also, the less eye gaze theyactually held on the faces that they were presented inthe experiment as well, too. now, when we have naturaloccurring experiments such as this, we don't really have control on preexisting conditionsthat may be there, genetic or environmental. so we've actually turnedto use mouse models
to try to see if we cancontrol for the genetic and environmental confoundsthat might otherwise explain what we're seeing. and so we borrowed paradigmsthat have been developed by individuals like regina sullivan at nyu and also tallie baram at uc irvine to, and do sort of a fragmented caregiving of a dam to her pups. and so i wanted to show you those movies.
on the top is a dam where we've taken away the nesting material. she has a little bit but not sufficient, so she is running around,oh, this is not in real time. (laughs) (audience laughs) she's a little bit slower than that. so basically, i don't even know if you can see the control dam.
so she has all the nestingmaterial she needs. and she's spending themajority of her time grooming and feeding, nursing her pups. but you can see the motherabove is trying to pull together the nesting materialand sometimes her pups over to her corner for the nest. so basically, you'reseeing this fragmented care because she can't attend to her pups when she's doing other things,
which we thought might,in the slightest way, mimic some of the fragmentedcare we see in the orphanages. and if you look within a two hour period, you see a significantdifference in the amount of time that the dam is spending with her litter relative to controls. but quite frankly, if youlook across a 24 hour period, they're spending almost as muchtime with physical contact, but it's very fragmented in that contact.
so there's not that attunementbetween the caregiver and the pup. so then, if we look attheir ability to regulate their emotions, not thedam, but now her offspring who've been given this fragmented care, basically, what we seeis a paradigm in which we've trained them that anozzle will lead to them having access to condensed milk. and mice love condensed milk.
and so we put that nozzle in a novel cage with a bright light where there'spotential threat for mice. and we see that when we put it there, there's a difference between those mice that grew up with the stress dam relative to the mice whose dam, theirmother, was not stressed. and you don't see any difference in terms of how quickly they move tothe nozzle in their home cage. and then if we look atthe brain using c-fos
activity as an index, we seeheightened amygdala activity in this group relative to the controls. and so this gives us a bit more confidence that what we're seeing in the human data that i presented is not as much associated with maybe preexisting conditions as it is with the early life stressbecause these parallel quite nicely. now, with the mice,unlike our human children
who are usually adopted by super parents, if you do nothing after that, you see that there's persistent affectsof that early life stress so that they're still showingheightened amygdala reactivity in adulthood even thoughthere's continued development of the circuitry. now this persistent effect in these mice is somewhat reminiscentof work that nim tottenham has done at columbia incollaboration with dylan gee
whose now a colleague ofmine at yale university. and she's actually shown that if you look at this frontolimbiccircuitry, that there may, there appears to be something similar to a premature closingof a sensitive period of neurodevelopment of this circuit such that if you justlook at healthy children, what i described before,there are drastic, significant changes from coupling
between the prefrontalcortex, and it becomes inverse or negatively related in adolescence. what we see in children whohave grown up in the orphanage is you're already seeingthose changes early. and so now, nim istrying to follow and see just how rigid doesthat make the individual when they go through adolescence, which is an even morestressful time of life in meeting so many challenges.
and i just want to endwith one more study, an area of work that dr.tottenham is following up on, and that is showing howimportant the caregiver is. and so, in these experiments,where we're showing these very simple stimuli in the scanner while we're taking pictures of the brain and watching how they perform games, if you simply put a pictureof the face of the caregiver along the screen wherethey're performing the task,
and you can counter-balancethat with a face of a stranger, she sees that that's associatedwith decreased activity in the amygdala, so it's adecrease in that emotional reactivity just by having thatparental cue present there. and also, there is an increasein the inverse coupling with the prefrontal cortex that is typical more of adulthood, butwe're seeing the parent has that ability to regulate. so i hope what i've shown youor illustrated is just one
small set of experimentsthat are being performed where we can show that early life stress can lead to persistentchanges in brain and behavior, particularly in termsof emotional capacities. and it highlights, too,this last bit of work, the importance of havingvery early interventions and also, the importance of the caregiver in helping to develop a healthy brain. and also, in terms of enhancingemotional well-being now
and hopefully, for that individual. so i just want to end bythanking so many individuals who have come through mylaboratory over the years, the majority of them fellowswho are stellar stars now. and to also thank you for your attention. - i'm really delightedto be able to participate in this wonderful symposium. what i would like to tell youtoday is one particular aspect that is absolutely essentialfor a normal brain development.
and that is to have proper parenting. we've heard from the wonderful talk from bj casey rightbefore me how important proper nurturing from caregiversis for normal mental health of the infant that then become adult. and so the question we'vebeen very interested in is what makes a parent a parent? if you think aboutparenting involve one, two, sometime multiple adultsthat take care of an infant.
the relationship iscompletely asymmetrical. there is really a very helpless individual that requires a lot, a lot of care for a very, very long time. and so what makes parents be parents? it's a, i think, a veryinteresting behavior, long-term behavior, that hasa lot of emotional components. and so this is a behavioralso that is displayed by many animal species.
it is absolutely essentialfor the development of and the survival of the species. so the idea is that theremaybe some genetically pre-programmed neurocircuit in the brain, and what we are interestedin is really trying to understand the neural basis. what are the specificneurons that are involved in the control of parenting behavior, in the display of parenting behavior?
and when is it that thisbehavior actually goes wrong? and there are a number of circumstances in which the behavior goes wrong. one, this is one of, ithink, one of the most outstanding, really impressive,or very surprising slide related to mental illness. that's the number ofpsychiatric hospitalization after childbirth. you can see right atthe time of childbirth
this enormous peak inpsychiatric hospitalization of women, and this arepatients that suffer from post-partum psychosis. this is very quite rare. it requires hospitalizationbecause these women have obsessive thoughtabout harming their child, their children, andtherefore, they require very intensive care. these very way less severe from,
which is post-partum depressionthat affect 10 to 20% of mother and 5 to 10%of fathers in the us. and this also comes rightafter birth and result in a inability to emotionallyconnect with children and in effect impaired parenting. now, there are quite anumber of risk factors: stress, life circumstances,prior depression, and sensitivity to hormone changes. as it turns out, right atbirth, there's an enormous
change of hormonal levelsin the young mother. you can see here progesterone,estrogen, oxytocin, prolactin is really anenormous and very sudden drop in hormone level. some people call these hormonal cows, and women, in particular,that are sensitive to these hormone fluctuationhave really a difficulty in coping with those changes. so how do we understand thepositive and the negative
regulation of parental behavior? well, let's turn to animals. so in animals and human aswell, the primary caregiver is usually the mother, and in animals, and in mammals in particular,this makes a lot of sense because in mammals, the mother nurture the fetus, the embryo,in utero for a long period of time an animal isinvolved in lactation, so really involve enormousmaternal resources
in nurturing the infant andtherefore it makes sense that mom continued to nurture the infant through parental behavior. what about males? well, in most mammalianspecies, a very large subset of mammalian species, the malesactually attack the infant. attack them sometime, or veryoften actually kill them. and this infanticidal behaviorhas been widely observed in many animal species.
and it is thought that this is actually an evolutionary-drivenaggressive behavior of the males in order to gain access to the females that are not accessiblewhen they are nurturing their own infant. and interestingly, this isa behavior that is absent in monogamous speciesin which both the male and the female are nurturing their infant and therefore, there is not this conflict
of access of the male to the female. now, infant neglect andaggression is also occasionally displayed by stressed female. this is seen in animalsas well as i mentioned in post-partum depressionand psychosis in human. now, we're not working with human. we're not working with primates. we're working with mice, and in mice, there is as in this animalspecies i mentioned,
a very clear sexual dimorphismin the behavior of animal, male and female towards infants. females even virgin females orsexual inexperienced female, spontaneously take care of infants. they will build a nest. they will lick and groomthe pups, retrieve them to the nest and huddle around the infants. virgin males in contrast willspontaneously attack infants, wound them, and kill themthrough infanticidal behavior.
so very different set of behavior. however, males are notalways infanticidal, and in fact, strikingly, malesafter mating with the female, are no longer infanticidal. and the video i wouldlike to show you here is from, if you wish, acertified infanticidal male. this male attacked infantsthree weeks earlier, and then, we had thatmale mating with a female. and then, we're testing the behavior
of this male now with these pups. and, as you can see, themale has built a nest, and now, is retrievingthese pups one by one, and i should mention by theway that these are not the pups of that particular male. this behavior will bedisplayed towards any infant that is, to which they are exposed. so all the pups are nowcollected to the nest, and as you see, this is a really good dad.
he is checking that he hasnot forgotten any pups. okay. nobody left. good. let's go back to the nest andthen take care of the pups. so this is a reallyfascinating switch in behavior that really indicate thateven in infanticidal males there's the ability forthese males to be parental. so how is this happening?
well, evolutionaryspeaking, this is actually not that surprising becauseif you look at virile animal species, insects,fish, amphibians, reptiles, birds, and mammals, they arespecies in which the female is always the one handling the progeny. you can see the little eggs here and little larvae over here. he's a tadpole on the back of that frog. but very similar species,genetically very similar,
show animal in whichthere's bi-parental care, so both the male and thefemale handle the nurturing of the progeny, and similarly,also very similar species genetically have the malethat exclusively takes care of the progeny. for example, this beetle herewith the little eggs here or this male amphibian with a tadpole or here this fascinatingmonkey, the titi monkey, in which the male is actuallyproviding exclusive care
of the infant. so what's happening here? well, in mice, what's happening is that there's a dominant malethat mates with the female and the female have a communal nest. these male is always parental. however, subordinate malesthat do not have access to the female, areinfanticidal will attempt to attack the male,kill the pups, and that,
in turn, enable themto mate with the female and at that time, they become parental. now from a neuroscience standpoint, this is fascinating because what it shows is that the brain hasactually two types of circuit. one driving infanticidalbehavior that is displayed by virgin males and one thatdrives parenting behavior that is displayed by females and fathers. so the question we are very interested in
is what are these neuronsthat control parenting and infanticidal behavior? and i would like to tell you today is how are we able to identify neurons that are necessary and sufficient to drive parenting behavior bothin males and in females? and so, what we use is away to identify molecularly neurons that are activeduring the certain behavior. and the idea is that when a neuron
is firing action potential, they're also changingtheir gene expression. and in particular, theyturn on a particular gene, a transcription factor called c-fos. and so if we have a female ora male interacting with pups, then neurons that are involvedin parenting will fire and therefore, they willexpress this gene c-fos. so if we look at thebrain of parenting animal, both males and female,compared to infanticidal male,
we find that there is asub-population of neurons in one particular area of the brain in the hypothalamus, an areacalled the medial preoptic area in which you see this verydense collection of neurons that express this gene c-fosafter the animal has interacted with pups, both males and females. so this is very interesting. it's actually not thatsurprising because already in the 50s, 60s, 70s, a number of groups
through lesion experiment haveshown that maternal behavior requires the function ofthe medial preoptic area. but what we really would like to know is which precisely, whatprecisely are the nature, the identity, of these neuronsthat are c-fos positive? and in fact, this area,the medial preoptic area, fulfill a lot of functions. it's involved in matingbehavior, thermal sensation. all sort of other functionsthan just parenting.
so knowing precisely andspecifically which other neurons that express c-fos is somethingthat we really need to know if we want to understand thecontrol of parenting behavior. so we tested the numberof candidate genes, and we found to our delightone particular gene, the gene that in code forthe neuropeptide galanin has been very nicelyco-expressed with c-fos when the animal are parenting. so interestingly, this,the number of galanin cells
in the medial preopticarea is identical in males and females in virginmales and in virgin male and mothers and father. in other word, these neurons are there in the male and thefemale brain irrespective of whether these neuronsare parenting or not. now, galanin is a peptideexpressed in many different areas. it has been involved inmany different functions such as nociception, sleep,thermoregulation, et cetera.
so we don't know whethergalanin has any role to do, to play in parentingbehavior, but the fact that we know one geneticmarker gives us genetic tools. in other words, we'reable to use a genetic line that express this enzyme called cre. think about the scissorif you wish that enable to activate specific molecular tool to manipulate the activity of neurons. and so the experiments that we've done
is to inject a conditionaltoxin into the preoptic area of the galanin cremouse, and what this does is that it enable us to kill specifically this galanin neuron presentin the medial preoptic area. no other neurons outside ofthe brain or within the mpoa. nothing else than the specificgalanin expressing cells are affected. what's happening when we test the behavior of females and fathers whenwe kill galanin neurons
in the medial preoptic area. the affect is very striking. the ablation of these mpoa galanin neurons entirely abolishes bothmaternal and paternal behavior. and actually, elicits infanticide. so there seem to be arole of these neurons, not only in driving parental behavior but actually inhibitinginfant mediated aggression. now, we try the other experiment,a sufficiency experiment,
which is if we now take an aggressive male and activate artificially galanin neurons in these infanticidalmales, what's happening? what's happening, and weperformed this experiment using a technique called optogenetics that enable to express alight-activated channel in the neurons and thenusing an optic fiber to activate these cells, and what we found when we shine light andactivate these galanin neurons
is that infanticidal malenow are longer infanticidal and instead display paternal behavior. so what it shows is thatthis specific population of neurons are bothnecessary and sufficient for the control of parental behavior in both males and females. now, the parental behavioris a complex behavior, and what we'd like to donow is really to understand this behavior in mechanistic terms.
so these neurons as we've seen are able to control parenting. parenting means a lot ofthings: grooming, licking, crouching, retrieving, nest building, and then inhibiting infanticidal behavior. but these neurons do all ofthis according, obviously, to the presence of an infant but also, according to the physiological state. male, for example, willeither trigger this behavior
or not trigger this behavior according to whether they are fathers or not. and so, what we wouldlike to understand is how are all these differentdisplays being performed and what is the role of this environment in the activity of these neurons? and the first set ofexperiment that we've done is really tried to understandwhether these galanin neurons really are involved inall these different part
of parenting. and so, the experiment thati'm gonna show you here is what is called bulkimaging or volume imaging of these galanin neurons. the idea is that theseneurons now are expressing genetically encodedindicator of neural activity. so these neurons are nowgonna emit fluorescence when they are active andonly in this particular area. and when we have an opticprompt that enable to visualize
the intensity of the signal. and so it's called bulk imaging because we don't have cellular resolution. in other words, we'relooking at the activity of all these neurons together. and so what you see here is a female and here a bunch of pups over there. and the animal has an optic fiber here and what you can see hereis the level of calcium.
and as the female approaches the pups, you can see the level of calcium going up. and she's licking the pups, and indeed the levelof calcium stays high. and then as she bringsthe pup to the nest, and start licking the pup,then the level of calcium is really going up the roof. interestingly, we foundthat all of the pups composing parental behaviorinvolved this galanin neuron.
so that's quite interesting. now, i'm gonna show you another video in which this femalehere has a very similar type of behavior as you can see. she's grooming something, licking, and then, she's gonna bringthat thing to the nest exactly as she has done with the pups, but as you can see here, the level of c level is completely flat.
what's happening? well, although thebehavior looks very much like parenting behavior, actually, she's handling a fishcracker, so that's not. and in these circumstances,galanin neurons are totally silent. again, although the behaviorlooks exactly the same, what's happening in thebrain, the significance of this behavior is completely different
and involved in verydifferent parts of the brain. so, in summary, we started by the idea that parenting is an essential behavior and that in different speciesit's displayed differently by males, by females, sometimes both, and that we were reallyinterested in going to the cellular and molecularbasis of this behavior. and we saw in this reallyinteresting system in a mouse in which animal are or not parenting,
and we found thisfascinating immunocell type, this mpoa galanin neuronsthat now really give us entry into how parenting behaviors control. what are the differentregulations of these neurons? what are their sets of projection? what type of input do they receive, and how all of these changesin both during development in males and females andduring mental illness. and i would to thank the people,the wonderful collaborator
in my lab who've performed this work. thank you. (audience applauds) - i tend to get unsolicited feedback, such so that should be a very short talk. isn't that a kind ofcontradiction of terms? you mean they found one? and there's like a book a month that sort of piles on inthese unflattering portrayals.
the primal teen, that'sactually not too bad, but mom, i hate you: get out of my life, but first, drop cheryland i off at the mall, now, i know why tigers eat their young, or right to the point,yes, your teen is crazy. but with the technologies such as magnetic resonance imaging,we can for the first time look under the hood atthe living growing brain. and what we've found is thatnot only do teens have brains,
but they're good brains. they're as they should be. they're not broken. and i'd go so far as tosay if they weren't the way that they are, we wouldn't even be here. evidence from that comes froma kind of unlikely source that i'll get to in a minute. so the teen brain's differentthan the brain of a child. it's different than the brain of an adult.
it's not just halfway between. it's, you know, kind ofits own distinct entity, and it's been exquisitelyforged by evolution to have certain features. behaviorally, the big threeare increased risk taking, increased sensationseeking, and a move away from parents to peers. and i think these are really deeply rooted in our biology cause it's not just humans.
all social mammals havethese three features. and so, we're probablyfighting mother nature by trying to eliminate these. and this is always veryspeculative to argue these ways, but one idea is that ithelped us get out of the home, which is a really irrationalthing to do, right? people love us. they feed us. they protect us.
it's a good gig, right? but it turns out it works better if we do. less inbreeding, it justsort of, not morally right or wrong, it just worksbetter if this happens. and so these features,they evolved at a time without firearms, without,you know, high speed motor vehicles, withoutdesigner drugs and stuff. some of these issues arekind of the stone-age brain in a computer age world aspect.
but i think that thesebehaviors have virtues as well. when i was i was a thenih, the smithsonian museum was sort of close. they had this exhibit,the hall of human origins, which i really like, but kindof not particularly featured. a little placard on the floorlooked at the relationship between brain size and climate change. and the last big increase in brain size, 500, 800,000 years ago, butwhat i thought was intriguing
was that what would correlateis the change in climate, not the degree. so before seeing this, i thought,yeah, it got really cold. you had to be supersmart just to stay alive long enough to get food and reproduce. but this is subtly different. everybody in this roomhad ancestors whose brains were good at adaptation. and were really good at it in terms of,
even compared to our quiteclose, genetically close, rather in the neandertrumpsor neanderthals. i'll pause. we can edit that later. and there's a, we can tellan enormous amount from teeth and fossilized teeth, whichis actually redundant. everybody's teeth right now are fossils, calcified cells, but they work like trees. so they have rings.
so tree rings you can,this was a wet year, a good year of growth,the rings are wider. and across many differentspecies, the rings get closer and closer as you mature. the rings stop, and you'redone growing, done maturing. and so when you findthese fossilized teeth, if you find a fossilizedneanderthal tooth of a 12-year-old, and then check the restof the cave, he's gonna be with his children, not his parents.
and this is often portrayedas surprisingly rapid growth in the neanderthals, but ithink that's the wrong way to look at it. what's surprising isour protracted growth. we're the outliers by far. it's one of the mostdistinctive things about us. and even across, like, crowsand many other species, the longer you're underprotection of your parent, the more complicated your food gathering,
your communication, youknow, problem solving. crows are actually reallysmart as an example, but similar crows in sizeand stuff that don't have this protective maturationdon't have those abilities as well. and it doesn't work tojust keep your kids at home 'til they're 40. i don't think on an individualbasis it doesn't work. it's an intriguing trade-off i think
that we keep options open. we keep our brains changeable,see what the environment's gonna to be like. we can live on the north pole. we can live on the equator. we can even live in outerspace for a little while with technologies that arebeing made and developed. and so this is a goodthing, i think, in terms of this ability to keepoptions open for a long time,
but it's really being put to the test with the digital revolution. and this is just in my shortcareer, it's a game-changer. in the way that we interactand like we're doing at this moment with onesand zeros and the lights, the projectors, you know,it's changed everything. it's changed the way that we learn. you know, content that's on internet. i mean, the greatest minds onthe planet are a click away,
for free. it's amazing. it's magical. the way that we play, andthe way that we interact with each other. and so, i've been fascinatedby this interaction in terms of the, you know,biology of this changeability and the technologies thathave taken over, in a sense, so of almost 11 hoursa day of screen time.
and 30% of that time more than one device. and so the usual questionis is it good or bad? that's the wrong question, right? almost any interestingquestion is it depends in terms of in whatways and how it depends and what it depends upon. but i think that this isan opportunity in terms of to influence adolescence. one of the tragedies of my profession
is that it's almost a 10 year gap between onset of illness and treatment. it's, we need to dobetter, and i think perhaps new technologies can helpus get there in terms of by monitoring things likesocial media activity. maybe even just movementto best aid harnessing these technologies in anethically appropriate way to help us recognize mentalillness so that we can intervene while the brainis still more changeable.
and so a lot of the debates around this that it's just not natural, right. we evolve to talk to eachother, to be with each other, share smells and touches and everything. and now, we're looking at screensfor a big part of the day. but a kind of argument to that is reading's not natural either. reading's only about 5,200 years old. so most humanity, nobody read.
so i don't think that byitself is a good argument. it kind of makes the point that the whole aspect of this is the changeability. 10,000 years ago, hunting,gathering berries, that's the same brain in terms of that's a blink of an eyein evolutionary terms. but our brains are amazing. we can adapt. a lot of us spend a lotof our day with symbols,
you know, words, and that, and that's so different than, you know, what our ancestors did. and so my career has basically been this in terms of trying tounderstand this plasticity in terms of how to optimize the good and minimize the bad. and this, kind of, how do you help people with mental illness isthe fundamental question.
and so, kind of thatnotion of what do we know? how do we know what we know? what don't we know? why don't we know that? but, you know, my first assumptionis the brain's involved. i hope so. if it's like the spleen orsomething, i'm gonna feel like a complete fool down the road. but i think, you know, that'sa good reasonable assumption.
and professor jernigan began this journey. bj and i started togethereach following down that path of looking at the brainand how the brain changes in both typical developmentand in illnesses. it's kind of a non-creativedesign actually. but scan kids, you know,when they're young, and follow them as they grow through life. see how they're doing at school, at home. see what sort ofinfluences are on the brain
for good or ill. and at the nh, we did about10,000 scans, half the kids healthy, half the kidswith different illnesses. and what we've found were, it's nuanced, but like, the brain doesn't mature by getting bigger and bigger. by first grade, it's already93% of an adult size. it matures by becoming moreconnected within itself and more specialized.
and this idea of being more connected, there's many ways you can approach this, but white matter is one of them. so this insulating materialthat you'll get one to two percent more of inthe fourth or fifth decade. the brain was able to communicateamongst itself faster. it's not very subtle. it's like a 3,000 foldincrease in bandwidth. it's, i think, underlies a lotof the remarkable behaviors
that we can do. but it's not just a matterof maximizing speed. it's all about the timing. and so fire together, wiretogether, the meaning, all the information in these patterns. but more and more we're understanding that's the progression, andif we look at different parts of the brain like letters of the alphabet, as we go from an infant tochild latency, teenagers,
emerging adulthood thatthese letters become words, the words become sentences, the sentences, you know, paragraphs metaphorically. and this all goes up in adolescence. the brain almost, nomatter how you measure it, whether molecular, eeg,blood flow, it's just, you know, it becomes more connected. and this is a kind ofa fresh look in terms of this idea of graph theory networks,
and it gives us a whole new look. so for something likeschizophrenia, before we'd be like, is this chunk bigger or smaller or a different shape or size? but looking at the samemri scan and the same data and looking at how it's interconnected, then we can discern old fromyoung, healthy from ill, cause they bring it back. not perfectly, but it's reallyexciting for someone like me.
i can't do the math, butto be a consumer of it in terms of that, by lookingat this connectivity, it gives us a whole newperspective on these illnesses. the other process isthe gray matter process. and the one, two punch isover produce and then war or fight it out, so it'show almost all complexity in nature arises. engine of evolution, overproduce something non-random selection, and it hasgreat, you know, potential.
so it's constantly ongoing. it's not like you only overproduce during childhood and only prune duringadolescence, but we see this upside down u type of curvewhere, as we specialize, the brain actually becomes smaller. so after around 10, 11, 12,your brain doesn't get bigger. it gets smaller but leaner,meaner, more specialized based on what is demanding of it. but it's not all parts equal.
the prefrontal cortex involvedin controlling impulses, long-range planning, it'sparticularly late to settle down. some 25 to 30, and thatcombined with the hormonally activated puberty activated limbic system, the path of rewards,this imbalance creates a lot of the specialnessof teen behavior aspects. but again, this is how it should be. if the prefrontal cortex was already done, like 11 or 12 and stuff, then,we wouldn't be as adaptable.
and so i think this is thetension or the trade off. the other place to start in terms of that, these illnesses happen atdifferent times and not perfectly. there's always variation, butalzheimer's doesn't happen when you're three, and autismdoesn't start when you're 60. that characteristically,certain illnesses tend to emerge at certain ages. and that's puzzling, you know. why is that?
in terms of, and when youstart looking at this, so much happens in adolescence. not a lot, most. so up to 75%, and i stilldon't know the answer. for 25 years, i've been like, why? because the early answer isoh, teenagers are stressful. it's stressful time of life. kids have their parentskilled in front of them or a lot are starving todeath in war-torn countries.
enormous stresses, but theydon't get schizophrenia. and so that never rang true. and i still don't know, idon't know the answer to this. why do things happen when they do? and so just one exampleis for schizophrenia. all of the findings yousee in adult schizophrenia, you could predict, whatif typical teen changes went too far? is not causal.
they already had schizophrenia. but it sort of, so far without exception in terms of both the mri changes but also the molecular changes. and so, it's just, thispoint, it's intriguing. it doesn't help me helpfamilies with schizophrenia. but i think these are the kinds of clues that we're starting to understand. so in the specialization process,
in typical development, it'sabout 7% from ages 12 to 17. in schizophrenia, 28%. so it's not subtle, youknow, a four fold difference. and so understandingthe typical development, i think is key, but abouthalf of what i deal with as an illness, isn't an illness, right. pregnancy is not an illness. but it's a big deal, right. relationships, car accidents,incarceration, you know,
life decisions, thishappens during adolescence. and it's frustrating,you know, as a physician, it's like there's noinsurance forms to check in terms of for these very real issues that aren't an illness. and this kind of notion,is the glass half empty or half full? because this changeabilitycould be a great opportunity making it even more tragicthat we aren't recognizing
the illnesses when they occur. and my final sort of analogyis to use michelangelo in terms of this is a veryfamous painting of his that by design should look like a brain, a cross-section of the brain. yeah, he wrote about it himself and stuff, and it's sometimes calledthe original synapse. you know? a little neuroscience humor.
but it's not like that. it's much more like his otherexpression of art, sculpting. and we start with this blockof marble and life experiences. so then, we eliminate parts. so me might be born withdifferent chunks of marble, from sizes, from genetics,but within each if we knew what we were doing, if wecould guide this process, you know, there's masterpieces. and, you know, in ithink almost everybody.
and we don't know very, wedon't know what we're doing yet very well, and it's like, mostof the illnesses emerging, less than one and a halfpercent of the funding has been adolescence. until now, finally, now,we have this project that for the first time isgoing to really do this right. 11, 12,000 or, you know, kids, 19 sites across the country tounderstand what matters. how does the brain growin health and illness?
looking at, you know, everythingwe can think of frankly, in terms of, influences on this. i'm gonna brag for sandiego a bit in terms of there's these 19 sites across the country, but the coordinating centerfor the quantitative core and the neuropsych corecoordinating all the centers are both here in san diego as well. what a good deal for us interms of the opportunities to try to understand, you know,
what matters in teen's lives. and so the technology is a big part of it. how can we get a better sense of internal and external environment with the sensors, with devices they're alreadyusing, they're already wearing cause this is the crossroads in right, this is where people, youknow, make big decisions about their direction in life. and there's this kind of notion that teens
are messed up and they'remisguided and stuff, and it's dangerous. i feel bad that i've, cause i've... oh, i see, people, i don't know. so this is in the crossroads. and what happens is even teens themselves buy into this, right. like stereotype threat and stuff. if you think that you're notcapable and stuff like that.
it matters. most teens do well. you know, they'll get through this. they'll do well. but i think we do adisservice by, you know, selling them short, andi think that, you know, we really need to recognizethe huge upsides of this. much more than the downsides. that if we can figure out whatwe're doing, what matters,
we can really make a big difference. thanks.
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