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00:02 So today we will be discussing neuronal And when we first talked about the

00:07 experience for example watching the we talked um precise uh like my cross

00:17 What all of these techniques allow us do is visualize unusual cells visualize individual

00:23 cellular components. This is a nice about grading spines about the great experience

00:29 visualized and reconstructed and this is all of the structure. So typically when

00:37 talk about morphology of the cells, of them rides anatomy of the dendritic

00:43 season. We're talking about structural imaging it doesn't have function in it.

00:50 when we talk about static or structural versus functional imaging neurons are functional.

01:00 increase their metabolic turnover rate, they a lot more oxygen, they consume

01:08 and there's increased blood flow to the of the active neurons. We're talking

01:17 imaging neuronal activity on the experimental neuroscience . We can image ionic flux is

01:25 there are guys that are sensitive to islands, calcium sensitive guys and they

01:31 show us fluctuations of calcium in different . For example, down drive

01:39 There are guys that are sensitive to islands such as sodium such as

01:46 So we can trace individual ion movement the cell specific ion movement. We

01:54 image neuronal activity and glial activity. we talk about neuronal activity, it's

02:02 , real activity is slow. So experimental setup with the demand for the

02:09 and the speed of cameras resolution might very different depending if you're imaging a

02:14 fast neuronal calcium flux is are much Uh What do you need image those

02:27 supplies of ions of calcium. They're fluorescent tags on the ions. And

02:34 the concentration of these ions goes the fluorescent signal changes, we can

02:39 image vault that you already talked about expressed all the indicators jetties. And

02:45 one of the papers you have and image single molecule like a receptor

02:56 An experimental nurse on. So we tag and pour some first and see

02:59 they move from the extra synaptic spaces the synaptic spaces. All of these

03:05 different imaging techniques that can be used now functional. So when you're talking

03:16 structure is one thing, but you're about flux is and ions changes in

03:21 , glucose consumption, calcium voltage These are all functional changes. Talk

03:29 the different levels that you go into uh supplementary uh reading here that we

03:41 . It's much better resolution. I'm and we talked about different levels in

03:47 you can measure and measure activity that described. The macroscopic club, messous

03:55 level. Macro is. You're looking a certain part of the brain

04:00 You're starting to understand what cells are to inhibit. There may be or

04:05 subtypes of cells are located and what function is. Circuit centric. When

04:11 starting understanding what are the subtypes of on the circuit how they're connected single

04:17 level and the sub cellular level. can look at the activity in either

04:22 spines and dendritic shafts or selma or . And then you could potentially compare

04:29 activity in different cellular compartments essential. within a single dendritic spine compartment,

04:36 can image activity quite successful. So is the experimental setup configurations for different

04:47 of this genetically expressed voltage imaging. way that we already talked about

04:54 The way that these molecules work is they get expressed in the plasma membrane

05:01 they have a fluorescent marker that is to the podium. And therefore it

05:10 gives you a signal, a voltage sensing signals. So it senses the

05:18 as it travels across plasma membrane. different iterations of these uh sensors and

05:26 molecules. But once you have that genetically expressed are applied on the tissue

05:34 can actually measure different levels. So can fix the head, right?

05:41 the animal's head is fixed. But imaging activity in the whole animal as

05:48 animal is performing a certain behavioral Would say the animal is smelling something

05:54 the animal is looking at something. . You can have in many instances

06:01 experimental setup in minusca. Oh oh like a little head microscope, Like

06:07 lens that get mounted typically has like optic wire that comes off the little

06:14 scope. There's an advantage here because animal is freely moving. So as

06:21 to being stationary and fixed head position reacting to certain stimuli. Now the

06:30 can move around with movement, there's with artifacts, there's problems with artifacts

06:37 experimental functional imaging. There's problems with in clinical functional image, such as

06:44 the person as the pet scan or . R. I. F.

06:48 . R. I. Scan. they move small movement can give you

06:55 . Sometimes their own diagnosis too. why movement is an advantage. But

07:03 you have to have a mechanism when doing these experiments to well, how

07:06 I gonna account for the movement? attacks, which ones are going to

07:11 movement artifacts And you're measuring activity And why does it matter because brain

07:20 is soft? So if you have on a certain level of tissue that

07:25 come out of focus a little bit there's different regional changes that happen as

07:31 moving, you can have a fiber . It's really interesting in a really

07:40 animal where you basically uh instead of local field potential recordings, you are

07:51 signals and selectively the signals by these indicators with this optic fiber. So

07:59 you're using optic fiber, like an , these voltage sensors will change and

08:07 gonna be able now to insert this and pick up the optical changes.

08:13 why it's likened to feel potential. likened to feel potential because it cannot

08:18 up activity from a single cell. accept activity from numbers of cells from

08:25 of cells. Okay now obviously you a higher magnification 20 X 40

08:34 You can have imaging in the circuits society capital Circuit, C. 01

08:41 one parameter cells and you can look it in the tissue or in

08:50 So if you have a stationary animal instead of the camera and this macro

08:55 you want to have a micro view could potentially do these experiments in vivo

09:01 but typically not freely moving. You're at the level of a single cell

09:09 circuit. So these are two very images to to review as as as

09:17 we cover this material. Let's look little bit about in an example and

09:33 brains and talk about a specific structure rodent brains for barrel cortex. So

09:41 rodents do is they are internal animals when they are out and about and

09:49 exploring they explore the environment by smelling . So olfaction and they will contain

09:58 very large or factor involved. So lot of the brain tissue is basically

10:05 to the primary factor information processing. way in which road and sense the

10:13 is the whisk around, whisk around they have a whisker pad and they

10:22 at certain frequency which is typically within low theater range like few hurts.

10:28 moving these whiskers a few cycles a and they're touching things the size of

10:36 walls, piece of cheese whatever they . So this is very important for

10:41 , the sense of olfaction and some sensation. Somatic sensation is especially from

10:49 . For us humans, it's a of sensation. If you want to

10:54 something, we use our hands And rodents will use their paws,

11:00 can move things with paws will pick up, but they will actually explore

11:06 of touching things whisking around and that that there's gonna be a lot of

11:12 area dedicated to the rodent whisker This is the whisker pad. These

11:20 the new brisa or individual whiskers is hair follicles and rodents typically have 12345

11:29 of whiskers on each side. The are not unique for whiskers actually have

11:34 dog and she has whiskers in funny like on her cheeks and like bottom

11:39 the neck, which is interested in . So, Madison's recording home

11:44 Um but you know, she's my . So I can't look inside her

11:51 , but here's the map for the in the primary somatosensory cortex of the

12:00 . And you can see that this brisa, the whisker pad. This

12:06 a huge area from the entire amount sensory cortex. It's dedicated to this

12:12 pad and it's really beautiful system because one of these whiskers in the primaries

12:20 sensory cortex has a barrel has a structure, anatomical structure where each

12:27 you can see 12345 rows of Each barrel here in this matter,

12:34 cortex will be processing information from grow from a single whisk. So

12:41 it's beautiful because you have this outside of rose, a number of whiskers

12:49 you look and you stay in the , medicines, the cortex in the

12:53 . And you see these barrels these as a precise exact number of barrels

12:58 a number of whiskers. So if rodent is missing a couple of whiskers

13:03 will also be missing a couple of , if they have an extra one

13:07 two whiskers, they may have also this matter sensory cortex an extra one

13:13 two barrels. So that information from bristle. When you're touching the whisker

13:20 , all of that information is traveling the trigeminal nerve. So all of

13:25 amount of sensory information from the neck and your head is processed by

13:33 nerve, five or trigeminal nerve and why this is called the trigeminal

13:41 So there are sensory nerve endings that , can imagine a simple fashion kind

13:47 wrapped around these nerve terminal around the follicles. So every time this hair

13:55 this hair this person moves and the follicle, the hair rooms inside the

13:59 follicle, it will activate the trigeminal . The trigeminal nerves that have the

14:07 branch, acts on that form the and send the information through the central

14:14 all the way through other structures, into the final destination of S.

14:21 which refers to primary amount of sensory or area S. One M.

14:28 refers to primary motor cortex. Area M. One and this once

14:34 demonstrates very neatly that if you have , 5 rose and a certain number

14:42 whiskers on the pad you'll find that anatomy in the cortex and guess

14:46 You can then move whisker two in C. Which is C.

14:52 And when you move physically that whisker . Two on the outside, you

14:58 see that activity in the barrel It's matter sensory cortex corresponding to whisker

15:04 . Two is significantly increased. This a really really neat experimental system because

15:11 can do manipulations that are very precise into single whisker on the periphery.

15:19 you can observe very precise map of in the primary somatic sensory cortex.

15:26 let's look through this image here. this is a single brief C.

15:36 . Whisker deflection and you can see this is C. Two. Whisker

15:42 . And you can see in the of medicines, the cortex first activates

15:46 barrel very small area for barrel And you can see the activity from that

15:55 area that expanding and spreading. So is the map of activity of brain

16:02 of activity if you may and when activity spreads. Now you're talking about

16:07 brain wave for that activity is traveling the interconnected networks in the brain and

16:16 into adjacent regions potentially into M1 Because as you move the whisker that

16:22 may want to move back is going be a motor control. So you

16:26 see activation here eventually of this M1 . So at first you have very

16:33 specific map that corresponds to just that Whisker that you're activating. And later

16:39 see a significant spread of that map that activity through the interconnected networks at

16:46 time. Why we should spreads is tens of milliseconds. Okay, so

16:53 activating a single whisker within 30:40 in will engage other parts of the

17:01 not just the primary amount of sensory through the interconnected networks through these brain

17:08 . Now this is A. Where we have a control experiment and

17:14 in the first condition we're wiggling whisker . Two. And in the second

17:21 we're stimulating whispery too. And you see that C. Two and

17:27 To reform distinct maps. You can that it's not the same barrel.

17:32 it's two distinct barrels. And later some 26 milliseconds time you can see

17:38 spread of the activity from C. and C. Two. Cool.

17:44 there are multiple experiments by which you manipulate the system. So you can

17:52 cut the whisker. And that's a cool experimental manipulation because it's not very

17:59 . It's not like blinding somebody. not you know you are cutting off

18:04 whisker and then you can see what anatomical changes of follow. You can

18:09 in this case block that C. whisker activity with C. N.

18:19 . X. On a Tv and . N. Q. X.

18:23 a PVR glutamate receptor blockers. So . N. Q. X.

18:27 an alpha glutamate receptor blocker signaling receptor an M. D. A.

18:35 a P. D. Is an . D. A receptor blocker.

18:40 if you block glutamate receptors happen in . D. A. By injecting

18:46 into the region of C. Two the sea to barrel column. What

18:51 do is you locally inhibit in the activity from C. Two. So

18:56 you stimulate whisker C. Two but don't see a map anymore. You

19:02 see a little bit of adjacent Maybe it's by adjacent whiskers being widely

19:09 . But then when you activate To whisker you still see that

19:14 Okay so now you wiggle see But you block the signals in the

19:19 locally in C. Two and you longer see the spread of this map

19:24 . So you can block the identity individual barrels and you can block specifically

19:32 zero whisker to and it will not zero whisker to. And the map

19:38 zero whisker to this is another way which these voltage sensitive dyes that we

19:50 be incorporated the plasma membrane. So kind of experiments that we're looking at

19:56 typically done with old sensitive dyes or another type of indicators that we discussed

20:05 , like calcium indicator. But we to do this a lot of times

20:12 imaging cortical activity. And if we're cortical activity we can image voltage which

20:18 to neuronal number and potential changes. it's really good. And this is

20:24 another way in which you can incorporate sensitive dyes into neuronal tissue. You

20:31 apply these as chemicals instead of genetically them, you can apply them as

20:38 make a window in the brain. can apply the dye on the surface

20:42 the brain. These dye molecules of quick little warms. They incorporate themselves

20:48 plasma membrane and as the voltage changes this is a sodium channel that conducts

20:57 inside or outside the south. Deep will cause a certain confirmation will change

21:03 these dye molecules that will indicate where strong activity. You will have read

21:11 it's weak or inhibited activity. You'll areas of blue and now when you

21:16 at this red and green traces you see these two red and green

21:24 . What these traces are comparing is comparing the imaging that is obtained by

21:31 fluorescence and electrical signal as the electorate implanted in the same region. What

21:39 observing here is it's 1-1 that the signal through the camera tracks precisely with

21:49 electrical signal that is recorded in the area of the brain. So intracellular

21:59 is blue and V. Is the activity is red. So it tracks

22:07 well with either the network or individual that is inside that network. That's

22:15 it's a great way to study neuronal changes because of the ability to do

22:22 at multiple scales. You now have ability to look all the way from

22:30 macro levels, all the way to cellular law office and because it's tracking

22:37 well with neuronal membrane potential changes for changes, it's a very valuable technique

22:47 study cells from single cells of cellular all the way to large areas of

22:54 brain and networks. And so when do imaging studies, we also reveal

23:03 structure the functional structure. When we anatomical studies we reveal that anatomical structure

23:11 reveals functional structure, function of these and structures equal function, function influences

23:20 , structure and influence of function. all independent of each other. In

23:25 end we have a lot of blood neurons, neurons will suck a lot

23:29 blood. But another very interesting and thing is that neurons that are

23:36 They're going to swell and as they , they're going to change the reflective

23:41 and you can image the surface of brain for what is called intrinsic optical

23:49 with both sensitive dies. There's a that you applied with genetically expressed voltage

23:57 . There's an indicator that you genetically with calcium, sodium potassium sensitive

24:05 you have to apply and die some of an indicator. The huge advantage

24:10 intrinsic optical signal. There is no that is applied. You're purely looking

24:17 the changes in the reflective properties of cells. And you can see here

24:23 called the striatum vortex of the primary cortex. And everywhere where you see

24:29 black lines of these blacks triumph that activation of one eye in the areas

24:35 are not uh lit up or shown darker colors of the areas that are

24:41 to the other. I this is the ocular dominance columns of the visual

24:46 . And it's a really neat way intrinsic optical signal to visualize these uh

24:54 dominance columns. Now you're its activity . So neurons have to be

24:59 There are disadvantages of this technique because can only imagine on the surface really

25:04 penetrate a couple of layers of the , but that's about it. So

25:12 is the cortical surface without that activation one eye. This is the cortical

25:20 . When you activated one eye and change the intrinsic intrinsic optical signal And

25:27 of the neurons and the primary visual responsive to that one, I then

25:34 you have is blood flow and this imaging of the blood flow. So

25:40 correlated to the increases in activity in region is correlated with the changes and

25:47 patterns of the blood flow to that . So more active neurons will do

25:54 demand more blood supply. All right let's uh before we go into the

26:05 . R. I. And things that. These are some of the

26:08 signal imaging maps. We already mentioned in the last lecture a little bit

26:14 uh welcome to read through this a bit. But it's a great way

26:20 image the visual cortex. It's a way to reveal the ocular dominance

26:25 And both of sensitive dye imaging and intrinsic signal optical imaging can be used

26:34 delineate the orientation selectivity. Uh this visual cortical cells. So it's it's

26:42 really it's a really neat technique again can image at the level of the

26:46 network and hone in with enough of uh image resolution using a two photon

26:57 imaging in this case. This is terms of signal imaging. In this

27:00 it's calcium imaging. You can reveal of individual neurons. That's really important

27:07 that you can have the underlying structure you image or sustain and use the

27:12 stain and apology stain but then you the image of the activity.

27:25 is the brain active all the What's happening with the resting states?

27:35 so this is from your textbook if go into a quiet room, lie

27:39 and close your eyes but stay What do you suppose your brain is

27:44 ? So now we're talking about the brain. Not anymore neurons, but

27:48 whole brain, If you answer is much, you're probably a good company

27:54 our discussions of various brain systems that how neurons become active in response to

28:00 sensory information or the generation of Modern brain imaging techniques are consistent with

28:06 view that in response to behavioral neurons become more active in cortical areas

28:13 process on the perceptual information. It reasonable to confirm that the brain is

28:20 in the uh in the absence of processing. However, when the brain

28:25 imaged with positron emission tomography. Now talking about functional imaging techniques that are

28:31 , such as that or F. . R. I. It is

28:35 that it is rest resting state. includes some regions that really fairly quiet

28:43 others that are surprisingly active to the in quiet states is not necessarily

28:50 it's just different parts of the brain important. Mhm. The imaging studies

28:58 the difference between the brain's resting state activity recorded while a person performs a

29:04 , they teach us an important lessons the nature of the resting brain and

29:08 functions that it performs the existence of state activity does not itself allow us

29:16 include much conceivably the resting activity might randomly from moment to moment and person

29:24 person, and activations associated with behavioral will be superimposed on this random

29:31 However, this does not seem to the case when a person engages in

29:36 perceptual behavioral task there are decreases in activity of some brain areas. At

29:40 same time the task relevant brain areas more active. One possibility is that

29:46 the decreases and increases in activity are to the task. So when we

29:52 at only the increases of activity that not be a fairly good representation of

29:58 of the areas of the brain that processing that task. In fact we

30:01 to look at the brain areas that go quiet for more quiet as one

30:09 of the brain goes more active which of the brain goes more quiet.

30:12 also should correlate to the activity. example the person is required to perform

30:17 difficult visual tasking ignore irrelevant sounds. might expect the visual cortex to become

30:24 active and the auditory cortex to become active. So we can have the

30:29 tuning and choosing stimuli. But what it getting at here? It's getting

30:37 . Maybe we need to understand the and brain status. Whenever we image

30:42 we stimulate we stimulate schaffer collaterals in . One and C calcium increases.

30:50 subject animals to sensory stimulation, we their whiskers so they're involved in active

31:00 and tasks and we're looking at these that are created by active tasks and

31:08 is this term sentinel sentinel is sort a term that in the in in

31:19 you're a sentinel soldier, your your is to keep the watch some sort

31:27 uh resting state. But it doesn't that the brain is to adopt.

31:34 means that different regions of the brain activated during the sentinel or arresting

31:42 Uh Conceivably, the resting activity might randomly from movement to movement persons.

31:49 does not seem to be the case bit to further observations suggest that there's

31:54 fundamental and significant about the resting brain . First, the areas that showed

32:00 activity compared to the resting state are when the nature of the task has

32:06 , it appears that the areas showing activity during behavioral tasks are always

32:12 addressed and become less active during any . Huh? So now we're talking

32:22 there seems to be brain regions that active when you are performing the

32:27 But when you're not performing the task this brain region is no longer

32:32 There's other brain regions that that are that are not involved in directly processing

32:40 that task. So, uh figure 1 summarizes data from experiments using nine

32:49 tasks involving vision, language and The blue and green patches in the

32:55 shown brain areas in which activity decreased the resting state when humans engaged in

33:00 of the nine tasks. Particular task seem to account for the activity

33:06 Second, the pattern in the brain changes are consistent across human subjects.

33:13 pretty cool. I thought we all differently but there seems to be some

33:18 replicable patterns across our brain. So why maybe a lot of us get

33:22 and think of like you know uh others that don't get along or think

33:28 . Maybe their patterns are a little . You know, these observations of

33:33 brain might be busy even in the we arrest that the rest of the

33:38 are consistent with these activities and Asked this perform the state of sentinel

33:46 or the state of internal meditation. you if you pay its cost of

33:53 now you will say why is this ? Why we're looking when we talk

33:57 E. G. We're looking for and outdoors. The E.

34:02 Technique is not very good for recording brain activity unless the person is performing

34:09 tasks. And you have all of filtering and measuring techniques to isolate certain

34:14 bands data gamma. That represent different . But other than that if the

34:18 is not having abnormal sexual activity, . G. Is not going to

34:23 much and it is not even There's no resting state. E.

34:28 . It's not typically done when you in right, they take your blood

34:32 and things like that. They don't a cap on you for 20 minutes

34:35 say what's your resting state? G. But maybe that is actually

34:41 important. It's just that we cannot that information from E. G.

34:47 not sensitive enough. We can start this information from imaging activity. Uh

34:55 imaging activity. And this is done pet imaging studies involving different behavioral

35:03 You can say that the brain have computer inflated activity in the south side

35:09 be seen. Brain areas colored blue green were more active during quiet rest

35:15 than during the behavioral tasks. So is more during the quiet periods as

35:22 to the behavioral tasks that were being . It's very important. What is

35:30 in any neuron inclusion. What is in learning and plasticity is prior

35:37 Its prior information of what happened was of what is happening in a resting

35:44 because what is happening in the wrestling will affect how the brain reacts to

35:52 . So but the brain and the maps are not quiet. It's just

35:56 the maps organization of the activity in quiet brains changes in three arranges

36:08 And this is uh an article that already looked at when we talked about

36:14 synaptic action potentials. E. S. P. S. By

36:18 dependent plasticity. And this is just beautiful image of the whole system here

36:25 the barrel cortex that we're talking in . So I have the soap and

36:29 on. Show it to you if guys wanna read through the figure legends

36:34 too. Now. Uh Oh that started talking about uh imaging techniques and

36:55 imaging techniques in particular uh different from broken bone. What kind of imaging

37:07 you do? But er excellent. you have uh if you have a

37:20 or computed tomography will C. Is is a sophisticated X ray

37:27 So what C. T. Does it uses a narrow X ray beam

37:32 the road. Very sensitive detectors that placed on the opposite side of the

37:39 . But essentially CT scan or computer tomo means a cut or slice.

37:48 a graphic of a slice. What is you can see that this X

37:55 source here and the detector. It be rotated, it can be rotated

38:01 multiple different focal planes and different angles you essentially target, let's say this

38:10 of the brain, you're interested in and you can send the deems this

38:16 and collect them on this side and you can send them this way and

38:20 the detector on this side and then can send them this way right and

38:32 them on this side. And what does is it really gives you a

38:37 nice three dimensional representation of that So you're imaging it from different angles

38:45 different slices through this three dimensional So you can eventually create it.

38:52 the X ray two brocades, three radio density matrix can be created allowing

38:59 to be computed for any plane through brain. So ct scams what they

39:05 do is they can readily distinguish between matter and white matter. It can

39:11 the ventricles very well and it can brain structures with the resolution of several

39:22 . So what is the diameter of single neuron? 10 Micro Fevers

39:30 So can I pick up single cell millimeters? We're talking about thousands of

39:37 meters. So you're looking at hundreds cells activity average from hundreds of

39:43 In this case it's not even activity it's hundreds of cells that are imaged

39:50 . That's the resolution. Mhm. now magnetic resonance imaging and the whole

40:00 imaging revolution that started with M. . I. In the 19 eighties

40:07 based on the fact that the FBI some Adams act the spinning magnet and

40:15 placed on a strong magnetic field. atoms will line up with the field

40:20 spin at a frequency that is dependent the field strength. So the magnet

40:27 produce a field. And typically these are strong Tesla 35 Tesla seven testings

40:36 can think about it. It's a bit of quantum physics that is not

40:42 really well understood of what the spinning happening. But it's like a

40:47 you know a toy that you uh going in the spinning spinning and then

40:52 can turn sideways a little bit is spinning and go back in this

40:56 This position tilt a little bit so what we're really are seen here in

41:02 . R. I. The magnetic is distorted slightly by imposing magnetic gradients

41:08 three differential access three different spatial access that only nuclear at certain locations that

41:16 to the detectives frequency at any given . So magnetic M. R.

41:25 . M. R. Images What can they do? They can

41:30 between very matter white matter cerebrospinal So it gives you more information.

41:37 if you had a tumor, if had a traumatic brain injury, if

41:41 had an infection in the brain that causing inflammation, what you would do

41:47 you would typically do to scan T. N. M.

41:51 I. And this is still not to show you any functions. So

41:56 have to do functional brain energy and do functional brain imaging which we talked

42:03 is detecting small localized changes in metabolism blood flow. You will have to

42:11 positive uh emission tomography, pet single emission, computerized tomography spect or functional

42:23 resonance imager. Now on the clinical , I have to tell you not

42:31 patient can go through em Ri scanning F. M. R.

42:36 Scanning those coils. You can see confining it is that you're measuring brain

42:44 you're being placed in this little A lot of people are have claustrophobia

42:50 they cannot go through this procedure. lot of Children can still stay still

42:58 lot of times if it is really to do this, they may sedate

43:02 patient. So anesthetized. But guess happens when you invest participation and you're

43:07 for brain activity. You changed his activity. So you're looking for tour

43:14 of the tumor with static imaging of or C. T. That's

43:19 But then if you're looking at M. R. I, then

43:22 imaging anesthetized basically with brain activity and is going to change a lot How

43:31 an hour, 20 minutes, depending the area that is being studied.

43:36 you're studying really small nucleus, maybe done in that machine 20 minutes.

43:42 you're scanning the whole brain for tumors something else, it's an hour,

43:51 ! People put headphones on spanking. really tells you that you're halfway

43:59 Uh And if I'm arai and I'm right, you do this and you

44:07 , in text scanning have a stable emission admitting isotopes incorporated into different agents

44:15 water rickerson molecules or specific neurotransmitters in and then injected into the bloodstream.

44:25 intense scanning what are the stable isotopes essentially labeled oxygen and glucose, Quickly

44:34 more metabolically active areas, labeled transmitter are taken up selectively to appropriate

44:46 So functional M. R. I M. R. I. Currently

44:53 the best approach for visualizing function best local tablets. F. M.

45:00 . I. Is predicated on the that hemoglobin and blood slightly distorts the

45:05 resonance properties of hydrogen nuclei in its and the amount of magnetic distortion

45:13 Logan has oxygen bounded. I don't know what these little fancy things to

45:33 . I want to visualize the whole presentation month. So here are some

45:42 the images and more images of adult with brain tumor. And then you

45:48 F. M. R. Activity during a hand motion task

45:54 This is a tumor and you can that it shows you the structure and

45:58 the pride is a three dimensional surface up of the same areas. So

46:07 resolution for F M R. 2 to 3 millimeters temporal resolution.

46:13 seconds. Maybe it's going to hundreds milliseconds. We were still talking about

46:21 , advantages of experimental imaging fast, sensitive guys, super fast kilohertz.

46:29 image of the killer hurt speed, herd samples, image sounds. What

46:35 your cellphone frames per second? 30 maybe 60 of the high setting

46:45 frames per second. So it's Right, 60 frames per second.

46:51 R. I F M R. . Uh you're talking about few

47:00 not so fast resolution, few How many cells? No single cell

47:07 . So it's an average of hundreds cells. And that Fox alert that

47:15 of imaging. So the changes in of oxygen and blood flow. We've

47:22 blood oxygenation level and the changes that called old changes. So you will

47:27 bold changes in F. M. . I. It's our situation levels

47:33 it is dictated by the blood you can see that you can have

47:38 nice three dimensional reconstructions advantage you can deep. So with that M.

47:47 . I. Uh that scan you image deep inside the brain all the

47:55 dyes calcium dies. If you have photon fluorescence microscope, you can go

48:00 little bit deeper into the tissue, a couple of millimeters to image.

48:06 you cannot image deep, intrinsic optical , circus signal to these disadvantages but

48:14 faster. So both the sensitive guy optical signal, you can imagine hundreds

48:20 frames per second tries to live your phone but in F. M.

48:25 . I. It's one frame every of seconds. Ultimately, what do

48:33 want Because we want to apply the uses of imaging functional imaging, we

48:43 to implement the same spatial and temporal scales in the clinical setting. So

48:53 we want to accomplish and you guys gonna be responsible for this a century

49:00 creating a very Good non invasive imaging . It can give you a resolution

49:09 you're seeing here on the order of mm area of interest but also give

49:16 an opportunity to zoom in and understand on the serpent level. That would

49:24 really cool or understand it on a cell is then out of these hundreds

49:32 thousands of cells in the area that is a normal task. You know

49:39 moving your hand as a normal task if you have abnormal activity coming from

49:44 part of the brain. If you it up with E E.

49:48 Now if you could apply F. . R. I showed that very

49:52 piece of the brain and is abnormally generating seizures. Now with Mariah have

50:00 of hundreds of cells. What if five bad cells? So then the

50:06 challenge is gonna be okay. So resolved there's five bad cells on the

50:10 that are called the seizures. How I gonna how am I gonna direct

50:15 therapy? How am I gonna take the five bad guys without taking out

50:20 hundreds of by themselves either pharmacologically or the surgeries or something like that.

50:26 how am I gonna do that? know? So it still is a

50:29 challenge. Even if we find our to single cells in this noninvasive clinical

50:37 we still are facing some significant Uh And and then therapy and how

50:47 manipulate the single cells with the small of cells tricks. Mhm. And

51:00 is just in just an abbreviation of we talked about. In fact you

51:05 be looking mostly at the oxy glucose glucose consumption. And then from ri

51:11 be looking mostly at hemoglobin oxygen There's a lot of really interesting techniques

51:20 are emerging in the last 10 There's M. e.g. magnetic electra

51:27 grant imaging. Um there is typically couple of interesting markers that can be

51:35 . Not just uh two D. . But there may be more specific

51:41 neurotransmitters. There are some markers that specific to alzheimer's plaques that we can

51:48 imaging. Uh Maybe even some blood that could be showing up in the

51:55 started. So this is a hot the bounce I feel. But as

52:00 know it's very expensive equipment. So example University of Houston does not have

52:09 F. M. R. Machine. Universities would have those or

52:17 of brain activity. Whole animal or . You have aged. Doesn't Medical

52:25 is multiple. But if you're doing procedure you want to have an

52:29 M. R. I. It's not like oh I can do

52:33 here and there and there and there every door I can walk in.

52:35 course you know this methodist will have own Andy Anderson call Sissy ball.

52:42 a lot of times it still is access to these machines. Still stand

52:50 line wait for three weeks. There's sign up. Uh And it's it's

52:57 challenge for humans. It's a Imagine you go get radioactive sit in

53:04 for an hour because you cannot be human being if you're doing a pat

53:09 you're ready to act that way and go in through machine for an hour

53:16 know and come out. That's Also when we see non invasive

53:24 Yeah, no electrodes being stuck in head. But it is but it

53:29 a challenging, challenging procedure. so that's all I wanted to tell

53:36 about imaging of the brain activity. again, I think it's important to

53:42 that the uh cellular level, we all of these guys forensic optical

53:49 which is not that great result signals level that you have all of the

53:54 specific guys. Guys. Really valuable the value. You can go across

54:02 different spatial scales from. So, their disadvantage if you're doing it in

54:11 slice, you're doing it in you're doing it in devo you're typically

54:15 to a small focal plane. The of the clinic. Again, you

54:22 get the same. You don't get start it. We can tell ourselves

54:28 to our military and maybe that is be the future. Right. If

54:32 can target to specific neurotransmitters, that be really cool. So now we're

54:38 about in general talking about these brain activities up or we call it it's

54:45 or its sentinel state were not But in reality, uh when we're

54:55 activity and neurons, it's related with but it's also correlated hyper polarization.

55:04 it'd be really nice to start taking this information on the level that we

55:08 that people did brain written studies like the micro lectures that did the triangulation

55:17 from individual cells and they can tell sell fired at which cycle of the

55:24 . But now it would be really if in these techniques we could introduce

55:29 and inhibition, dermatologic signaling and the temporal dynamics of these separately. Not

55:38 , you know, active brain And so So next time when you're

55:45 , you know, and in don't go by that urban myth.

55:49 we only use 10% of our Always say that you could probably use

55:55 than 10%, which is probably not . Uh and it's also not good

56:00 have 100% of your great views because called generalized seizure. All of the

56:07 is fully active. All of the are fully engaged. So what we're

56:12 is that there's a switch off going active during the task. These regions

56:20 up in active, this goes down region, activity comes on. And

56:27 I'm also saying is that it's very to start understanding this baseline sentinel

56:32 That may inform us something about the for that network too hard. Sentinel

56:39 would be like what is the sentinel of the heavy and and ground.

56:45 if you know the sentinel state of N gram, you can predict how

56:50 stimulus is going to recreate that the state of the heavy engram would be

56:59 state of neurons in this interconnected circuits active somewhere inactive and depending on the

57:08 of the training supply to this, this graph. Now you can understand

57:14 is active in sentinel state and how sentinel state will affect the end ground

57:21 the stimulus as well. And that's becoming important in seizures and epilepsy,

57:27 a lot of times people throughout the activity or what happened before the

57:34 So they would just analyze, oh can see the seizure happen here.

57:37 let's take the data a minute before seizure and the minute after we see

57:43 stopped at E. G. analyzed us emphasis, logical what's really

57:51 importance these what happened before seizure How what happened before the seizure to

57:59 ? How long was the seizure? , thank you. And when we

58:06 back uh next week monday we will covering the visual system and talk about

58:17 critical period of plasticity and development and into the retinal, articulate pathway meticulously

58:23 move into the sun some of the systems to optimist. All right,

58:30

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