Brain Games that Capture Brain Circuits and What Neuroscience Tells Us about the Self

this program is presented by university of california television like what you learn visit our website or follow us on Facebook and Twitter to keep up with the latest UC TV programs tonight you're gonna hear three talks from three members of the memory and Ageing Center which is actually just right across the street and Sandler neurosciences so first I'm gonna talk about brain games that capture brain circuits specifically how to use brain games to make inferences about memory systems and after me you'll hear from Bree Boettcher she's also a neuropsychologist at the memory and Ageing Center as I am and she's going to talk about the evidence for using brain games to improve your cognitive function and lastly you'll hear from one of our neurology fellows Winston Chung who's gonna talk about neuroscience and philosophy so I think it'll be an interesting evening so in my talk I hope that you'll learn that there multiple distinct memory systems in the brain and by using carefully designed cognitive tests we can measure separately how well each of these systems are functioning during the first half of my talk I'll focus on the distinction between working memory and long-term memory consolidation I'll start with the story of a famous patient known as HM who taught us that there are multiple memory systems in the brain then we'll try out some tests of working memory and long-term memory like the ones that we use at the memory and Ageing Center and last I'll end with that section I'll end with some tips about how you can maximize your memory function using these insights from neuroscience during the second half of my talk I'll focus on the distinction between a low centric and egocentric navigation memory strategies so there's two major ways that we can navigate how we can find our way around without getting lost and I'll ask you which strategy do you prefer to use at the memory and Ageing center the most common reason why new patients come to us is because they have a memory problem when a patient tells us that they have a memory problem we ask them to give us some examples and when we ask this question we get very different answers so here are some of the most common answers that we get I have trouble finding words or names when I need them sometimes I can't remember why I walked into a room especially if I get distracted on the way I forget where I put my keys or part to my car I can't remember the meanings of words or even what objects are used for I sometimes forget what I did yesterday or last week and even when I am reminded I sometimes can't remember these are all very different memory problems and in fact they rely on different memory circuits in the brain we learned that there are different memory systems from a famous patient who is known as HM HM had a seizure disorder that was not well treated with medications and so his surgeon dr. William Scoville performed a bilateral medial temporal lobe resection cutting out the middle parts of his temporal lobes including the hippocampus on each side you can see in the figure there on the left in HMS brain there's a big chunk of brain that's missing so the good thing about this surgery was that it cured his seizures but it had a horrible side effect he could no longer commit new events to his long term memory he actually lived a long life I need see the same doctors sometimes day after day and it was like he was meeting them for the first time so HMS was impaired at laying down new memories long term memory consolidation this is the type of memory that we often mean when we talk about memory it's what we use when we're a student and we study a subject so that we'll remember the information later it's memory for facts and events it seems to have almost an unlimited capacity one of the important findings with HM was that there were memory functions that were spared so we know that the medial temporal lobe is critical for long-term memory consolidation from hm but we know that it's not critical for some other memory functions for example HM was able to learn new skills we call this type of memory procedural memory like learning to dance the salsa or learning to ride a bike it becomes a habit after a while you don't even really have to think about it you just remember how to do it almost effortlessly so this is called procedural memory and it's subserved by very different brain circuit than the long term memory consolidation short-term memory was also relatively preserved in hm it's also called working memory because we use this kind of information to hold small amounts of information in our mind so that we can work with the information this type of memory is very temporary and has a very small capacity so good these two types of memory were preserved in HM despite the fact that he had those big chunks of his medial temporal lobe removed so HM taught us that there are multiple distinct memory systems so I'll talk a bit more now about this short-term or working memory it's the type of memory you're using right now to listen to this talk and process it in your mind and think about how the stuff you're learning may apply to you or people you know you're processing or working with this memory as you listen so working memory holds information and conscious awareness so we can use it the information can come from our senses like right now you're listening to me talk and that information is going into your working memory the information can also come from your long-term memory stores the duration is seconds it only lasts up to maybe 20 or 30 seconds unless you keep rehearsing the information over and over again in your mind for example if someone gave you set a phone number to you and then you walked over the phone to dial it you would hold that phone number in your working memory so that you could remember it when you need to dial on the phone but if someone distracts you when you're on your way to the phone you're likely to use it and that's because this working memory has a very limited capacity and so distracting information can compete with the information you want to pay attention to and then you can lose it so it can only hold about five to seven items in your mind at a time which is perfect cuz phone numbers are about seven digits long or nine digits if you can chunk the information you can hold on to it longer so for example if you recognize an area code in the phone number you can chop that and it becomes one unit and then you only have to remember the other seven digits so the better you inhibit irrelevant information the more information you can hold in your working memory now I think this is why people who are under a lot of stress have trouble with their memory they may have a lot of distressing thoughts that are interfering with their working memory so there's not enough room in their working memory for what they want to pay attention to so good strategies for improving your working memory are to reduce your stress and also just try to reduce distracting information if you need to concentrate on something or concentrate an important conversation try to do in a quiet place with fewer distractions so let's try a working memory test I'm gonna administer to you a very popular neuropsychological test of working memory I'm gonna say some letters and numbers to you all jumbled up and I want you to say them back to me with the letters in order first followed by the numbers in order okay are you ready all right f3 a8 all right good let's try a longer one now kw9 2p all right good so that's the test of what we would call verbal working memory where you have to hold online those letters and numbers and manipulate them reorder them in your mind so now let's try another test of working memory that we're using in our research right now I want you to remember the last three locations that are shown so this is a test of spatial working memory it turns out that spatial working memory and verbal working memory the test we just did have some similar neural underpinnings but also have some separate neural underpinnings so for example some patients might be impaired and spatial working memory but not verbal working memory or vice versa in Alzheimer's disease early on working memory is actually pretty good but the type of memory that they have problems with is the same type that HM had problems with long term memory consolidation why is that well you can see in this healthy control brain this is the hippocampus it's nice and tight and plump and lots of neurons there but in the Alzheimer's brain there's a lot of black which is the cerebral spinal fluid that has come in to fill in where the neurons have died so this is an early target of Alzheimer's disease and this is why early in the disease many patients have trouble laying down new information into long term memory stores they may have trouble telling you what movie they saw last week for example well let's try a test of memory a test of long-term consolidation so I'm gonna read a list of words to you I want you to listen carefully and when I'm through I want you to say them back in your mind in any order and if you want you can try to keep track of how many you're remembering on your fingers or tallying but don't write down the words okay so I'll read the list of words to you and then you can repeat them back to yourself when I'm done in your mind arugula paperclip Apple stapler telephone gorgonzola Scissors red onion I'm finished repeat them back in your mind ok let's try it again let's see if you could remember more this time it'll be the same list arugula paperclip apple stapler telephone gorgonzola Scissors red onion okay we administer a test like that one to all the patients who come in our clinic and what we find is the first time we read the list of words the Alzheimer's patients perform pretty similarly to controls so this test actually I think has 16 words slightly it's a different test than the one I just gave you but it's similar and at trial 1 they repeat back a similar number of words but then over the learning trials we actually administer 5 learning trials you can see the controls get better every time every time you remember more words and this is because their hippocampus is helping them to consolidate the information but in Alzheimer's disease they don't show as much improvement over the learning trials because their hippocampus is not as effective at this and importantly over the long delay which is 20 minutes we see that the Alzheimer's patients remember almost none of the words in fact many of the patients don't remember that a list had been read to them so this is a problem with long term memory consolidation how does the hippocampus consolidate new information into long term memory stores well it consolidates the memories in a widely distributed network of brain regions in neocortex so for example let's say you went to an important family wedding several years ago well the brain doesn't just consolidate your memory of that wedding into one node in the brain and it's connection to hippocampus rather it consolidates the memory in a widely distributed network of brain regions the same brain that you used when you process test the information at the wedding so the same brain regions that processed the sites of the wedding and the taste of the cake the sound of the music the conversations that you had there the emotions that you felt there those same brain regions are involved in the memory for the event emotion in particular seems to be a really important organizing force for these memories so these nodes in your brain that represent the event are all interconnected functionally for this memory and connected with the hippocampus and every time you recall that wedding over the years these same regions are active and interact the hippocampus is critically important for bringing up that memory over time however the hippocampus becomes less and less important for bringing up that memory so many years after the wedding the hippocampus may not be important hardly at all for bringing up that memory this is why patients with Alzheimer's disease can remember better events from earlier in their life then the movie they saw last week they may be able to tell you stories from their childhood but they can't remember that you went to a party with them last week and this is because the hippocampus is less important for recalling memories from earlier in your life then for more recent events so we've talked about the brain circuits important for memory and the differences between short-term memory and long-term memory consolidation what can we take from all of this to maximize our memories well I'm going to leave you with two tips here the first is we remember when we pay attention so when you focus and you reduce distractions and the second is we remember when we make it meaningful so when you make associations that give new information context or significance in terms of all the other things you have in your mind the reason this works is because memories are stored based on the Earth's their associations to other events or memories so let's try this technique out so brie is someone you're gonna meet in a few moments she's gonna give the next talk and I don't know about all of you but sometimes when someone introduces themselves to me I hear the name and I'm second later it's gone so I encourage you and when someone tells you their name to stop a moment and focus and make associations so for brie you might imagine a plate of brie cheese right and just think about how delicious that cheese is and imagine brie eating that big plate of brie cheese you'll probably never forget her name again and if that doesn't work I have an even better strategy for you you can think of someone else you knew by the name of Brie maybe there was a girl back in high school with the name of Brie and let's you know even better let's say that she stole your boyfriend so you just you remember that girl brie who stole your boyfriend remember emotions are very powerful organizing force for memories so if you can activate your emotions while you're trying to remember something you're much more likely to remember it alright let's try another one so Winston Winston is gonna be giving a talk on philosophy and neuroscience later this evening and I think it's gonna be really good talk so you could remember you know Winston he's a real winner or you might think of Winston Churchill you know Winston Churchill was always smoking cigars so you might visualize Winston smoking a cigar so the more you engage your different senses I find visualization in particular to be helpful the more likely you're going to be able to remember new information so we've talked about short-term memory and long-term memory and how to transition information into long-term memory and again the tips I have for you are one stop and pay attention and to make associations as we consolidate long term memories in terms of their associations to other memories or concepts the most effective associations are original even absurd they engage multiple senses they engage emotions or there personally salient so before we shift to the second half of the talk I'll just review the brain basis of these two memory systems so the short-term memory or the working memory relies principally on the frontal lobes and frontal parietal circuits but the long-term memory consolidation relies critically on the hippocampus and over time the hippocampus lays down memory throughout neocortex and and after many years the hippocampus isn't even really that critical to recall the memory so now I'm gonna move to the little talk on navigation memory so I want you to think for a moment how will you find your way home after this talk if your GPS isn't working there are two primary strategies that we use to find our way around the first that I'll talk about is the a low centric system which means other-centered when we use this system we represent where locations are relative to major landmarks in three-dimensional space we often anchor our allocentric cognitive maps in Cartesian coordinates north south east west for example if you are using the alo centric navigation system you might think my house is north of UCSF between Coit Tower and Fisherman's Wharf so you're appreciating the relationship between these major landmarks in space your allocentric cognitive map of San Francisco does not change if you are at UCSF if you're at the Golden Gate Bridge if you're in New York City it's the same map it doesn't depend on your position in space this system relies critically on the hippocampus more so on the right hippocampus in the posterior portion so in contrast to the allocentric system the egocentric system is self-centered when we use this system we chain responses with local cues for example you might think to get to my house I take a left on Third Street I take a right on King Street and follow along the water after I pass the Ferry Building I take a left so you can see with this system you don't have to appreciate the relationship between these locations in three-dimensional space you just need to know when you get to the Ferry Building you take a left this type of system is very efficient when you've navigated along the same route so many times that it becomes routine but let's say you're going to work on the same route that you take every day and there's a detour well you're egocentric system isn't going to work anymore and you need to pull up your allocentric cognitive map to come up with another way to get home so this system this habit learning system relies critically on the caudate nucleus which is a structure in the basal ganglia deep inside your brain the reason we know so much about the neural circuits important for navigation learning is because if you want to know how a rodents cognition is working you put them in a maze and you see if they can find their way out or get some food so when when people are looking at rodent models of Alzheimer's disease for example they evaluate how well the treatments working by seeing how well the rodents can find their way out of a maze so this is the most popular cognitive test for rodents it's the Morris water maze on this task the mouse is put into a cloudy cold pool and the mouse is swimming around trying to find the hidden submerged platform so he can escape he does this over many trials and the platform is always hidden in the same place however the rodent starts from a different position on every trial so the only way to get better and better at finding that hidden platform which he's sitting on right now is to learn the relationship between the hidden platform and the cues that surround the pool in three-dimensional space just like you know the relationship between quite Tower and the Golden Gate Bridge and UCSF when you pull up a map of San Francisco in your mind so we've developed some virtual reality tests of those two navigation strategies that we're using in our lab because we think that they're sensitive to different brain circuits and are disrupted by different diseases so I'll show you a couple examples of these so this is the human version of the test I just showed you we actually have a version of this test outside and I invite you to try it after the talks so on this test you drive around in a circular field looking for the buried treasure when you drive over it it will appear so you have many trials to find it and for you to get faster and faster at finding it you need to appreciate the relationship between the external cues the houses and water tower mountains and so forth and the location of the buried treasure just like the mouse had to learn where the hidden platform was relative to the cues around the pool so we think this test is very sensitive to hippocampal system dysfunction and we're finding that it's particularly impaired in the earliest stages of Alzheimer's disease which targets that system I'm going to show you now another test that we're using this one to measure specifically the egocentric navigation strategy on this test the subject navigates through a long route through a neighborhood it's always the same route and you learn it by trial and error each time you get to an intersection you take a guess about which way you think it goes and if you get it wrong you're prompted to guess again until you get it right over time subjects get much more accurate at this test and it becomes almost a habit for them so to do this test well you just have to chain responses with local cues when I get to this cactus I turn right for example so we think these two types of navigation memory are really tapping different brain circuits in in our brains and that they're affected by different diseases I think we all use both of these strategies but I think some of us tend to use one more than the other so think to yourself you know which strategy do you tend to use there are actually some sex differences on these tasks as well and you men tend to be a little bit better on average on the allocentric navigation paradigm although I definitely had some some women volunteers who have done amazingly well and one explanation for this comes from evolutionary psychology if you think about hunters back in prehistoric days they had to wander long distances through winding paths to try to search for prey and find their way home they really needed to rely on that allocentric memory system so I'm going to finish now with some take-home points there are several types of memory we focused on the distinction between working memory and long-term consolidation as well as the distinction between a low centric and egocentric navigation memory each type of memory relies on a set of brain regions and circuits by measuring the function of different types of memory neuropsychologists can make inferences about the integrity of the different underlying brain circuits why is this important why do we need to understand the links between memory and brain circuits well memory disorders tend to target specific circuits and so to treat these diseases we need to understand how these memory systems work and why they fail also even healthy people can benefit from these understandings they can maximize their memories by understanding how memory systems work thank you all right good evening everyone as Kate mentioned my name is Bree Boettcher and I also often introduce myself to patients by saying that it's like the cheese and feel very fortunate that I wasn't named after Gouda so I'm gonna be talking to you tonight about something I think is really salient to all of us which is forestall and cognitive decline so preventing any decline over time in our thinking all right so just to begin I think one of the main questions that dominates our field is how do we slow the cognitive aging process and by cognitive aging what I mean is this typically gradual decline in our ability to process and manipulate information quickly and this isn't restricted to middle or older age we actually start to experience declines in how quickly we process things pretty early even after our 20s and so in terms of the research landscape I think what has been most remarkable in the past few years is a transition in focus so for quite a while we've had an anchor in looking at preventing dementia and this still is a very important focus of our work but over the years particularly the last decade there's been even more focused on staving off decline so not even necessarily dementia it's just preventing any cognitive decline and in addition to that I think in the last couple of years we've seen a lot more information a lot more media buzz around remaining cognitively robust throughout our life and maybe even improving our cognition I think this a Newsweek article actually there's a perf on personifies this interest that's developed over the past few years of how do we maintain our abilities and can we even get smarter over time so transitioning from doctor post singh's talk on spatial cognition and verbal memory I plan to talk a little bit tonight about cognitive plasticity and brain games and I'm also going to follow it up with a brief discussion of physical exercise so how physical activity is related to brain health and what are the mechanisms by which physical exercise might actually impact our thinking so just to provide some context for how this evolution and aging research has transpired I think it's really important to examine early studies of plasticity and cognitive reserve and they would have really the most striking examples of this comes from the early nun studies which I think some of you might be probably familiar with we talked about a little bit last year the nun study refers to this longitudinal study of Catholic sisters they were members of the the school sisters of Notre Dom congregation there's actually a book on this topic and this included approximately it was a little bit over 650 between 650 and 700 Catholic centers were enrolled and their ages ranged from 75 to 102 years old so when the study began in 1991 and what was great about this study is that the sisters received annual examinations and they all agreed to donate their brains upon autopsy donate their brains for autopsy upon death probably an important distinction there so the son study provided this really controlled means of evaluating predictors of cognitive resilience and also cognitive decline in a group of individuals who clearly had very similar lifestyles so that we didn't have to worry about you know any multiple partners across the lifespan any exposure to particular diseases you know it's a pretty clean sample though that they they had to look at and from this study the researchers led by dr. Snowdon at the University of Kentucky reported several important findings and I think has really changed how we think about cognition over the lifetime and one of these findings includes the observation that some nuns had brains that were riddled with Alzheimer's disease pathology but did not show any manifestations of a dementia and dr. Snowdon reported several case examples so including one of sister matthean there to illustrate the individual differences he noted in pathology and clinical manifestation so sister mithya reportedly died at 104 years of age relatively healthy dementia free and upon autopsy they noted that the severity of Alzheimer's disease pathology and her brain was at around a stage for suggesting that there was moderate spread of a disease in her brain including the areas that dr. Poston mentioned that are very important from memory namely your hippocampus so stemming from this research is the question of how there can be such heterogeneity in clinical outcome among individuals have a pretty similar degree of pathology in their brain so importantly I think it's important fact to highlight that what we see under a microscope does not always reflect what we see in everyday life it's not necessarily a one-to-one correspondence so when you examine individuals with the same severity of Alzheimer's disease in their brain some may show Alzheimer's disease related to related dementia and maybe clinically normal with no dementia and so the question really is why is this and how can we tip the scales towards clinically normal with no dementia right and one theory that has led to an influx of research on cognitive exercise and training it's a theory of cognitive reserve and cognitive reserve was propagated by dr. Yaakov Stern he's at Columbia University and he developed this idea to account for the disparity between the degree of pathology someone has in their brain and their clinical presentation so what is cognitive reserve it really relies on the idea that there are individual differences in how tasks are processed that permits some people to cope better than others with brain changes brain pathology damage or degeneration so in the face of aging or even Alzheimer's disease pathology a brain with higher cognitive reserve may try to cope with impending changes by using pre-existing cognitive strategies more efficiently or they may flexibly use different strategies for the same task so kind of reserve is really hard to measure because in many ways it's a it's a theoretical construct so we can't measure it the same way that we measure plaques and tangles in the brain because of that researchers often rely on proxy measures to assess cognitive reserve so this would be something like educational attainment how far you went in school your occupation your mental activities which is sort of a nebulous term and your IQ so consistent with what we saw in the nun study this also suggests that individuals with more cognitive reserve may be able to tolerate or handle greater amounts of damage to the brain where for clinical impairment is evident I think the figure here illustrates this model nicely as it shows that at the same level of brain pathology individuals with higher cognitive reserve are performing much better on the same tasks so an alternative way to look at this is that individuals with higher content only start to approximate the lower levels of performance when they have more pathology in their brains and there's been a tremendous amount of support for the benefits of high cognitive reserve and I think what's what's nice about this conceptualization is that it's an active model so it doesn't assume that you need a certain amount of change to your brain before you start to show difficulties in everyday life and instead it focuses on the processes that actually allow individuals to experience these changes and still maintain a similar level of function what's also helpful I think about the recent data is that even late stage interventions to improve cognitive reserve look promising so that could ultimately delay or even prevent dementia and this is I think really intimately related to that concept of plasticity which really relates to the brain's ability to modify its structure and its function in light of new experiences that we have all right and I think a natural extension of this topic is that of cognitive exercise and brain games so translating the cognitive reserve and plasticity research into interventions has been kind of a difficult process I would say and there is an extensive scientific literature that is messy and difficult to interpret so brain games Sudoku and intellectual engagement have been heavily fed to the media as this sort of ultimate panacea for for cognitive decline I'm sure most people here I've seen these in the mainstream media before and I should say that some of this has occurred without research supporting it so what do we know about these things there has been some encouraging results in terms of leisure activities that were reported in the last couple of years and they've shown that people who have high rates of intellectual leisure activity which they define as things like reading books going out to operas playing games at home playing cards taking a new class that all of these were protective and that individuals who did this had a cognitive decline it started much later in life that individuals who did not report doing these activities and so we're still a little unclear about the mechanisms by how this works but there has been some promising evidence to suggest that even intellectually leisure activities might be helpful similarly there's been a lot of buzz and rightfully so about cognitive interventions these findings have also been mixed and with some studies demonstrating a lot of benefit and then some studies showing absolutely no benefit and I think this is where being an educated consumer is critically important particularly given the sheer volume of brain games that are being marketed to the mainstream public so on one hand we have studies that have shown no benefit from brain games and by no benefit I mean that when individuals are trained on these tasks they do get better on these tasks but that it's not generalizing to other things to other important activities in someone's life so for example and a study reported in nature back in 2010 researchers randomly assigned over 4,000 people to two different experimental groups where they were being trained on things like memory tasks or reasoning tasks and then a control group and they completed training sessions over a period of six weeks and while again like I said they they show significant improvement in the tasks that they trained on they did not show any transfer of benefit from that and that's really what you want you really want to have transfer of benefits other things in your life for these to be most meaningful so that's one side of the coin I think on the other side what we're seeing is in the last couple of years there have been very encouraging studies that have been coming out and I think what's different about them is that they are training people on very targeted cognitive processes so they're very specific about what they're training the individual on and it seems like that's probably most important in terms of reaping the cognitive benefits so the findings are promising but mixed and I want on the positive side I want to give you an example from some studies that are occurring at UCSF and these are going to be talked about little bit later in the interactive portion of the night so this is dr. Adam Cazalas lab and dr. Ann Guerra who also works with him and has really spearheaded some of these studies we'll be here in the interactive portion to talk with you about these so for these studies the ghazali lab in collaboration with colleagues at LucasArts they have developed this game called neuro racer and as you can see here it's a I mean I think it even just looks really exciting when you see it and so this is really thinking about cognitive training in the context of single task versus multitasking and I think multitasking is something that comes up a lot for people as something that can be difficult over time so in this study they are doing some pre-testing where they have people come in and they they do some tests on them and then they have people go home with these laptops and they do trainings at home on this task and then they come back in later and do some more testing in the laboratory so and these tests are really designed to emulate multitasking in everyday life while controlling for specific cognitive processes so you can see here what we have is the there's a single task version and there's a multi task and with the single task they have is a sign that the the participant will have to respond to while in the multi task they will still have to respond to that but they're also driving a car and so again to really emulate the kinds of things that we're dealing with on an everyday basis and from this they calculate a multitasking cost so what is the cost to your performance just by multitasking and it's a fairly really basic calculation that they use there so using the index shown before you can see the cost of multitasking increases across the lifespan so in other words the ability to efficiently handle and respond to multiple sources of information worsens over an individual's life and you can see this actually starts even in your and your 20s now these results start to look very different upon providing more to tasking training so specifically individuals who did not receive any training remained at around the same level a month later individuals who obtained the single task training at home so again they were trained on just responding to those signs without actually driving the car their performance um it looks a little bit better this is not statistically significant and then those who were trained on the multitasking component you see this striking difference and in striking improvement in terms of how much cost there is there and most importantly what we see is that these actually hold over time and so after a period of about six months you're still seeing much better improvement with individuals that were taint over trained on the multitasking component so again dr. Iyengar will be demonstrating this latest version of these games on an iPad during the interactive portion of the night okay so just to briefly review the cognitive engagement and brain games section of this I just wanted to say that in terms of plasticity and cognitive reserve I think there's really strong evidence that our brains continue to change and adapt that's part of what plasticity is and research I think has really uncovered a lot of protective and risk factors for this and in terms of the actual brain games I think as I said there's a lot of new research suggesting that if it's targeting specific cognitive processes that's the most helpful and this is I think a really promising area of research but also requires a critical eye and in thinking about the fact that not all of these studies have a lot of research behind so being an educated consumer about this I think is one of the most important facets of it so something that I am increasingly excited about is the role of physical exercise in brain health in a particular how exercising might actually improve cognitive and potentially delay or even prevent dementia so what have studies shown in general what we've shown is that what's good for your heart is good for your brain so individuals who participate in physical activity particularly aerobic activity they're shown in various studies that you can have up to 30% and a reduction in the risk of cognitive decline and dementia I wish I think it's a very striking and exciting finding cuz it's something that we can do something about at any stage and in particular just to answer that question Christine Yaffe and dr. Middleton at both UCSF and the San Francisco VA have conducted studies trying to answer the question doesn't matter when you become physically active so is it too late to start if if I didn't if I wasn't doing any sort of activity as a teenager is it too late to start in middle or late life so what they found was that women who reported that they had been physically active particularly during their teenage years showed the lowest likelihood of cardio impairment so they seem to be the most protected however individuals who became active later in life also showed a reduced risk of developing cardamom pyramid so even though it seems like a lifetime of physical activity is most helpful people are reaping benefits from this even if they start late in life to become physically active so it seems to be a really critical component to brain health so in addition that was more of a what we call an epidemiological study on cognitive decline so what if we turn our attention to what the brain looks like in those who are physically active so research with animal models has shown that a molecule in the brain called brain derived neurotrophic factor or BDNF is critical for neuron health and is really important for plasticity or synapses and exercise has been shown to have a really robust effect on B Nia BDNF levels in the brain so in this case if you have rats run on a wheel for as little a week what you can see is that they have a nearly a one-and-a-half fold increase in BDNF expression in their hippocampus and these effects were also still noted so they were still raised three months later in these animals and so you can see here that there's this induction of BDNF in various parts of the hippocampus so that's the dentate gyrus this is the CA 3 in CA 1 regions if we kind of try to take that literature from animals and apply it to humans we're also starting to see some really exciting results and this study came out in the last year and this was looking at 120 adults who were randomized to either a walking group or a stretching toning group and these groups are completely identical except that the walking group participated in moderate intensity walking for about 30 to 45 minutes per day three times per week so they both groups received the same amount of social interaction and health instruction so they really controlled for a lot of variables here and then brain MRI scans were conducted before randomization after six months and again after the completion of the one-year trial so if you can see here that what they were really focusing on was the hippocampus hippocampus is a very metabolically active area that seems to be very sensitive to plasticity and where there's been probably the most research in terms of plasticity so that's where they were really focusing on the caudate and the thalamus were also regions that they looked at more for control areas so with the hippocampus what they noted was that for the individuals that were in the stretching toning group they had about a one-and-a-half percent decline in their hippocampal volume over the one year and this is very consistent with normal aging research so this is something that we often see when we're following adults over time but in contrast what they found was that individuals who were in this more aerobic lee active group that they actually had a 2% increase in the size that in Pepa camp is particularly the anterior part of the hippocampus over one year and this was a significant difference in the two so this is one of the thing with one of the first studies to robustly show this in a regimented way so these observational studies along with others provide considerable support for the hypothesis the hypothesis that physical activity may reduce the risk of cognitive decline and dementia but how does this actually happen I think this is an important question to ask anytime we're reading literature about something new is what is the possible mechanism behind this how could this possibly happen how does this confer benefit and as you might guess physical activity is related to lower rates of obesity like I mentioned before what's good for your heart is good for your brain so obesity particularly middle age has been shown to associate significantly with dementia in later life physical activity is also linked to reduced vascular risk so again anything having to do with your cardiovascular system blood being innervated up to your brain it has significant benefit for any sort of vascular risk factors that someone might have so this could be diabetes hypertension cardiovascular disease and as I had just mentioned before it also seems to induce BDNF which is incredibly important for neuronal function and something that's more near and dear to my heart is its relationship to inflammation which is something I study in healthy older adults and people who are very physically active seems to have lower levels of inflammation in their in their bodies an inflammation has been shown to be related to your brain structure in particular what we have shown is that inflammation people who have higher levels of inflammation so they're just healthy people who do not have cognitive impairment but if they have higher levels of inflammation they seem to have lower integrity in the white matter areas of the brain and so if you can see here actually the white parts here the and the green traps these are these are not clearly what your tracks look like but they are color coded here and you actually have lower integrity and something particularly called the corpus callosum that connects the two hemispheres of your brain together and this seems to be highly related to inflammation so people who are physically act to seem to have lower levels of inflammation so in terms of lower integrity we we use something called diffusion tensor imaging which basically looks to see how well does water molecules move across a track and if something is really intact like if you think about any sort of anything about a fiber or anything that's a really attack track things should move along it very easily if it's starting to degrade at all you'll have lower directionality of the water you can think about water just starting to spread out and so that's how we measure that so it seems like it's unclear exactly what's degrading necessarily if it's the outer sheath of it but it seems like there's lower the structure of it doesn't seem to be quite as intact as it was before these white matter tracks are really important for processing information quickly so they connect all these different parts in your brain the the gray areas that connect these so that you can think more efficiently all right and so just to start to conclude a little bit what I want to really highlight here is that based on this evidence with physical activity I think it's pretty clear that there's considerable evidence that you can reap the benefits of physical exercise at any age and it's actually what we tell our patients the most often I would say in our clinics is that this is something that you can do at any point in time and it will really benefit your neuronal health as well as benefiting cardiovascular health and I think there's also ample evidence to suggest that exercise really reduces vascular risk factors obesity inflammatory markers and may alter brain structure as well so I think the combination of these these cognitive training cognitive exercise and thinking about physical exercise are two very tightly interwoven facets of how we can improve our cognitive health of our time and hopefully stave off dementia all right so I just want to thank my colleagues and I really appreciate everyone's attention and letting me talk to you about this topic and I really look forward to speaking with you afterwards in the in atrium there so moving in a slightly different direction my name is Winston Chong I'm a neurologist and neuroscientist at the memory an aging Center and I bring a sort of an interdisciplinary perspective and that my PhD was actually in philosophy and one of my areas of interest is actually in kind of points of contact between philosophy and other kind of more humanistic disciplines and clinical medicine and neuroscience so what I'll be talking about today is a little bit more speculative but I really try to take a look at some points of contacts and recent findings in neuroscience and how we might use these in connection with some older ideas to think a little bit more about what makes us kind of uniquely human and kind of what contributes to our sense of self so I hope you'll bear with me on that so before I talk about the self though I wanted to start by talking about kind of a more general principle which is the idea that brain diseases tell us about how the healthy brain is organized that when we pay attention to what goes wrong when something goes how it happens in the brain that that tells us that gives us important clues about how things are connected in a normal function and one of my favorite examples of this actually comes from this passage from the Bible which many of you will already be familiar with but after tonight I hope after you leave you'll think about it in a slightly different way so this is psalm 137 from the King James Version and this is after the conquest of Jerusalem by the Babylonians and what's interesting about the psalm is that it describes two kind of divine punishments that the speaker would wish upon himself if he were to forget about Jerusalem and they're the two punishments are let my right hand forget her cunning and let my tongue cleave to the roof of my mouth and so if you think about this either of these in its own right would be a very severe punishment right so for the first one we're talking about essentially losing the use of the hand that 90% of us used to do pretty much everything and we're talking about the loss of the ability to speak and so you might think originally well this seems like a bit much I think why should it be both why should they happen at the same time but I think that what's very striking as a neurologist when you read this is actually but these two problems off come together we actually do tend to see people with both of these problems at the same time and I'm assuming that the ancient Israelites observe this also so to understand why it helps to take a look at the brain so this is a picture of the brain from the left side so if you're looking at my left ear if you could see through my skull this is what you'd see and I wanted to call your attention to a couple brain regions so this region here in yellow is what we might call a motor speech area and among other things that's done by this areas basically it helps us to go from words to the actual movements that you have to make again you know with your lips your tongue and so forth and one thing that we don't think about because we're all fluent speakers of a language is what a skillful and coordinated action it is to speak because basically you're talking about coordinating the movements again of your jaw your lips your tongue your vocal cords your breathing to produce each word and ordinarily you don't have to think about how to do that and that's partly because the sort of motor program for how to perform all of those actions correctly is kind of stored in on the left side in this sort of yellow region then close by along this red strip there's another region so you may know that the left side of the brain controls the right side of the body the right side of the brain controls left side of the body and so along this red strip is a region that controls basically the movements of the right hand so the neurons in this region send signals down to the spinal cord that in turn send other signals down to the hand and basically control those movements and so you can imagine that if something happens to the brain here that it's likely also to affect this region and vice versa and in fact if you take a look at the map with the blood supply to the brain there's a very important blood vessel that comes up through the neck comes into the skull and basically gives off this branch that supplies this whole region so something were to happen like a blood clot were to migrate or develop here you can easily see how it would affect the blood supply to this region of brain so this region of brain would be permanently injured leading to loss of the ability to speak as well as loss of the movement of the right hand and it's sort of fitting I think to me that we talked about this as a divine punishment or in a theological context because you know our English word stroke which is you know the modern term we use for this disease when you have a blood clot that blocks this vessel comes from the term the stroke of God's hand right so this express again the idea that this is a sudden devastating loss of neurological function and while the ancient Israelites probably did not know that this is the way things were connected we can learn from this observation that you know has been made for a long period of time that this is how these parts of the brain are connected so that's I just an illustration that I like about how we can learn from these brain diseases about how these things come together even if we didn't know about the brain itself so this is the way we've learned about a lot of a lot about how particular parts of the brain work do we take what we call these focal lesions these diseases that affect particular parts of the brain so strokes tumors dr. piscine talked about side effects of brain surgery and so we've learned in this way about how these particular parts of the brain are important for functions like vision language memory our control of a movement or sense of touch and so forth what is kind of a new frontier though in neuroscience and this is what I want to talk to you about today is a little bit more distribute in the brain right and that's the question about how do these parts all work together right how are these different functions brought together to make us who we are because we're not just language we're not just vision we're all of these things brought together and the suggestion I'm gonna try to present today is the idea that it's really the coordinate activity of multiple parts of the brain working together and there's something we can really learn about how the brain is organized kind of in this way so here we're getting again from sort of more hard clinical neuroscience to something that's a little bit more ineffable a little bit more intellectual and philosophical maybe and starting to talk about again the topic for tonight which is kind of neuroscience in the self and I think one of the problems that we have as a starting point is just the observation that when we talk about the self you know people use this language in a lot of different ways and seem to referring to many different things that you know might be related but you know it's helpful to think about these differences and so one thing that philosophers like to do is to kind of cattle the ways that people use natural language and so if we think about different ways that people speak about theirselves we can identify maybe hopefully a few themes so obviously the self the idea the self is very related to ideas of individuality right so myself yourself and also there's this difference between self and others right there's sort of boundary where I end in the rest of world begins we also see this you know in immunology when we talk about your immune system is recognizing self versus other another step that's related to this is the idea of reflexivity or reflectiveness that we think about self-awareness our ability to take ourselves as kind of the object of our thought or perception and then there's a lot of ethical ideas right so there's an idea of personhood that there's something special about beings that are cells that have a self there's a relationship to identity and this is the problem that kind of most philosophers would think about in terms of the problem itself and that's kind of almost the problem of what makes you the same person over time right so you're you today and you know there's also you you know five days ago or five years ago and you know what's the connection between them that makes it all a continuous shared life share itself and finally you know there's this ethical idea of autonomy which again we go back to the Greek roots is really giving a law to yourself that could being the kind of being that you know can self legislate in this way and so what I'm going to suggest today when I try to translate this language into sort of more the language of neuroscience is that these different senses are related to again more global processes not things that one particular part of the brain does but rather these more general processes that integrate the activity of these different parts of the brain so if we take again our lesson that brain diseases tell us about how the brain is organized then one thing that we might look to for inspiration is to think about brain diseases that are not like strokes or tumors but brain diseases that affect many different parts of the brain at the same time and I'm going to get into a slightly controversial area and I hope I don't get myself into too much trouble but there is an idea that dementia is a disease it's very threatening to people's self and I say it's controversial so you know there are some people that say that this is something that happens so here's a popular book for family members of patients with Alzheimer's disease and the title of the book you know what suggested yes this is something that happens this is something we see that you know family members need to know about that patients with Alzheimer's disease you can can lose their their self in the course of the disease but at the same time you'll have other people who say no how could you say that right the self isn't lost in Alzheimer's disease itself endures in Alzheimer's disease and what I'm gonna suggest in part is that some of this controversy reflects actually different neurobiological and neuro scientific aspects that are related to the self that might be might be preserved or might be lost in these different diseases so hoping to broker a compromise sorts on this so I'm gonna unfortunately introduce a little bit of philosophical jargon but I hope it'll be helpful thinking about us as people as agents that have to move around and be effective in the world and make sense of the world there are two kinds of problems of sort of integration right so we talked already about the different functions that these different parts of our brain do but they've got to be brought together in a coherent way that allows us to deal with the world and to be effective in the world and two problems in particular that I want to focus on the first I'll call a problem of synchronic unity and by this I mean unification of kind of your activity at a given point in time and the first observation to make is that at any point in time there are hundreds of different things that are all competing for your attention right so you might be trying to pay attention to what I'm saying but you might find your mind wandering to think about what kind of cheese are gonna be serving the reception afterward or you know how can I get my hands on one of those brain games and in addition there's also kind of sensory information right so you're listening to my voice you're looking at the slides but you might also be distracted by you know an HD feeling on your leg or the way the tag of the shirt is rubbing against your neck things like that and your brain is being bombarded by this information all the right all these things are actually being represented in your brain these things you know are happening but you know you can't be responding to all of those at the same time and similarly from the point of view of motivation we all have conflicting aims and desires that can't all be satisfied at once right so you came here to learn about the brain to learn about brain games and so forth but you know you might have also hoped to go to a movie or meet some friends for dinner and so forth and you know we know that we can't satisfy all these different aims and desires at once it again so in both cases you've got to focus you have to prioritize and allocate attention and that's just you know in any given moment then in addition there are problems that all call the problem of diachronic unity and that's kind of being here in sense across times right because you know your your life extends far beyond this moment far beyond this room extends forward and backward in time and we all have important plans and projects that extend over the course of our lifetimes or when we think about things you know for the sake of our children or important causes we have we actually have important projects and plans that extend beyond our own lifetimes right and so part of being human is kind of this ability to you know think about yourself extended beyond the present moment you plan for the future and then in order to do this you've also got to be able to recall prior intentions right so you signed up for this course maybe a week or two ago and then you had to remember today but today was the day are gonna come you've also got to be able to keep track of different things that you do in order to realize these long-term goals so yes I already did step one and step two and then now I have to think about step three and step four and some psychologists have suggested but one way of thinking about this task that we all have as human beings is in terms of a faculty they call mental time travel right and so that's kind of the ability to project your perspective and you know to imagine yourself kind of in the future or in the past and we use this when we recall old experiences when we think about you know particularly moving experiences that we had in life but it we also use it when we think about the future so you know maybe you've never been to Barcelona before but you'd like to go and you can imagine yourself walking along less ramblas or standing at the base of less Familia and looking up at the spires right so it's it's helpful that I have to see two problems of the self because there's also two different forms of dementia that I think might be relevant as disease models that tell us about the way that you know again we think about the way the brain is organized in health and we also think about the way that things can go wrong in the case of disease and so one of them Alzheimer's disease is one that you've already heard a lot about one that may be less familiar is this disease called frontotemporal dementia yes those of you who are like here last week would have heard a lot but a lot about it as well but you know these diseases tell us actually about different brain systems that seem to be involved I would suggest in these different aspects of self integration these different kinds of Integrative problems of the self so patients with frontotemporal dementia these patients are very very unique they're very tragic in that they really have an inability to make their actions coherent particularly you know it's just even in the moment so these patients were often disinhibited so these patients are prone to do things like you know they might see people in the supermarket complete strangers and say that that they're fat or that they they would like to have sex with them and you know one thing I would say is that you know these are thoughts that even in normal people might occur to somebody in the course of their interactions you know kind of being out in the world but you know we know not to say these things and and sadly these patients don't have that ability anymore these patients could be very distractible so even when they're focused on a particular goal that can be easily distracted and so they wind up doing something else they have a certain loss of concern for other people loss of empathy that might be connected more broadly to a loss of a sense of kind of the importance of other people they tend to perform a lot of compulsive and repetitive movements they might tap their leg in a certain way or we've seen patients that rub their skin raw because they just have a tendency to rub in a certain way or they might make repetitive kind of vocalizations like in a certain way that can be kind of very inappropriate to the setting they kind of overeat so if there's food in front of them they're likely to eat especially sweets something I've put in grey because it's not part of our formal criteria anymore but it's something that we use clinically is a loss of insight so these patients seem especially unable to reflect upon kind of the changes in their personality and the ways that the their behaviors affect other people so that's front a temporal dementia and then you know we've also talked about Alzheimer's disease and you know two of the things that we've already talked about are you know that they kind of forget these episodic memories so they kind of lose the ability to lay down these memory traces and refer back to them and as dr. piscine pointed out they also have trouble even in learning and acquiring these memories these patients are often disoriented in time so they lose track of the day of the week the month even the year and they also have difficulties navigation right so these patients don't get lost in time but they got lost in space so these patients tend to wander they tend to lose track of where they are so one of the things is that that's important to know about these diseases is that they don't just strike sort of randomly they actually tend to occur in patterns and they affect different parts of the brain but they're they're quite repeatable in in terms of which parts of the brain these particular diseases affect and so here I have a map in in blue might be familiar to those of you who are doctor Seeley's talked last week but you know there's certain parts of the brain that are affected in certain parts that are spared in front of temporal dementia and similarly for Alzheimer's disease and then what's quite interesting is that when we go back and look in the healthy brain we've done a lot of research that looks at these sort of networks that are distributed across the brain so again not asking about what one particular part of the brain does on its own but more research that's devoted to how these different parts of the brain are connected and so we've identified these networks but when you look at them there's you know a significant amount of correspondence between the areas of the brain that are affected that are atrophied and lost in these dementia syndromes and these networks that we see even in the healthy brain and we're calling these the salience network and the default network so so I should say that that while Alzheimer's disease affects the hippocampus as was mentioned there is actually this broader constellation of brain regions it's also affected in this disease so for the salience Network when we look at this network that suspected in front of temper dementia and we ask what are we learning about what this network does in healthy people we're finding that it's related to a lot of the functions that you might guess just based upon our knowledge of the disease so we know that reaches this network are very important for things like value what value we attach to things even the value of things like money or relationships emotion there are nodes of this that are very closely associated with motivation and drive with you know kind of the will to get up and do things then even very basic cognitive processes like paying attention and being alert or staying on task or all related to this network and are all very closely related to deficits that we see in patients with these diseases on the other hand we know from again studies of healthy people that this default network is important for things like autobiographical memory and envisioning the future so these are things that we would relate again to this idea of mental time travel a couple other things that the default Network seems to be involved with that may be related one has to do again with navigation with certain kinds of tasks were you know we have to orient ourselves in space the one that's also interesting is adopting other perspective so imagining myself in your shoes knowing the things that you know and which might be different from the things that I know this seems to be involved and also mind wandering which might be actually tapping into some of the memory and envision the future right so when your mind wanders you're often likely to think about maybe something that you're doing a conversation we're having yesterday or you might find your mind wandering to something that you'd like to do in the future and kind of a broader picture that includes the idea of mental time travel that some people have proposed is that this default network is involved in engaging in these sort of dynamic simulations of possible states of affairs so that you know when we recall a memory one thing that we do when we kind of reconstruct that experience is that we draw upon you know things that we've stored in the brain to recreate the experience that we had of that memory and that we might use a very similar system you know when we think about something we're gonna do in the future so there we're not drawing upon memory per se but we use a similar system along with information that we already know about some future then that allows us to simulate it in a similar way so in conclusion I've talked about two distributed networks right so again we're moving beyond thinking about things that any particular region of the brain does in isolation and instead thinking about what the coordinated activity of these distributed parts of the brain do together and these networks seem to be very central to the activity of other parts of the brain and I think that you know when we think about what what is the upshot of this for us you know as of as human beings that you know the function of these networks seems to be to give some coherence to our thoughts our motivations and our actions and my suggestion is that this problem that I've mentioned have synchronic unity of kind of being a unified Asian at a particular point in time you know able to kind of deal with all of the potentially distracting information the conflicting desires that we haven't and so forth you know it's really something that is served by the salience Network and meanwhile that this problem of diachronic unity of being an agent that's extended over time that's agency can go and kind of back and forth beyond the present moment is something that's served in part by this default Network and then getting back to the controversy that I mentioned before if people were to ask the question you know is the self lost in dementia I my suggestion would be that the answer this question we really have to distinguish between different kinds of unity that are important to being a coherent coordinate itself so I think that you know one thing that we definitely do see in Alzheimer's disease is a loss of unity a loss of self across time right so these are patients who have trouble linking one moment to the next you know and so it can be very very difficult for these patients you know to make plans or to rely upon their knowledge of past events and being effective in the present in future but you know we also know that these patients can be very very present in the moment these patients can be very sensitive to other people's needs and emotions you know they can respond and very socially appropriate very graceful ways to all kinds of challenging situations and you know this is I think what a lot of people refer to when they say that you know this is the preserved part of the self in Alzheimer's disease meanwhile when we see patients with front temporal dimension I think one of the things that's very striking about them is this loss of unity and coherence even at a given time so just in a single interaction with one of these patients you might find that they're distracted that they're emotionally disengaged they acted in somewhat bizarre ways but you know if they're paying attention their memory of these past events and their ability to project forward and backward can be preserved and so you know so I think that in overall I'd say that you know when we think about these different diseases we might think about different aspects different tasks of kind of self integration and see ways that they can stay together or come apart you

Channel: University of California Television (UCTV)

Views: 128,619

Keywords: neuroscience, the self, Winston Chiong, Brianne Bettcher, Kate Possin

Id: eK3T5UIwr3E

Length: 78min 34sec (4714 seconds)

Published: Wed May 08 2013