Neuroscience of Pain & Pleasure

[In Editing Mode: will be updated by the end of the month]

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Hi everybody, welcome to neuroscience of pain and pleasure. Before we begin, I'd like to introduce you to the concept of what we call as alert and resting states of brain. We have uh we when we talk about a resting state in brain, it does not mean that we do not have any processes that are running on the back end. That means there exists something called as a default mode network that is constantly running in the background. It is only and only if a stimulus that is salient enough gets triggered uh ends up

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triggering your salient network. That's the only time wherein you have alert states of brain. The physiological version of those alert states of brain is arousal. When we look at brain imaging studies, the areas that light up is what we refer to as an aroused state of brain. It has nothing to do with your vaginal arousal or your penile arousal or any of those things. It has got more to do with how much of oxygen is going into which parts of the brain and which parts of the brain are well turned on at

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this moment. The reason why I go into that is a lot of pain perception of a lot of our pleasure all of these things have a lot to do with how it it's context dependent. It has a lot to do with how much of our senses are actually triggering some kind of perception in the brain. So for context, how many senses do you all think there are? We have some 20 plus, we have five, six plus. Do we have any other answers? Well, we generally when we are talking about senses, we refer to these five, right? The visual, alactory, auditory,

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gustatory and tactile. We also sometimes refer to intraception, proprioception and vestibular systems. However, there are 32 senses. Now, the reason why I bring this up is it is almost always associated with some or the other type of sensory processing disorders. Given the fact that any amount of change in our perception of these senses is automatically termed as a disorder. However, if you do apply some amount of um social uh science uh definitions of disorders, something can be categorized as disorder only and only if there is a

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system that is not designed to accommodate you in that system. That is the only time when something can actually be processed as a disorder. The reason why I bring all of this up because is it when we talk about pain, when we talk about pleasure, when we talk about anything with respect to the brain, there are so many ways in which things get processed, so many ways in which things can be interpreted which is completely different from well the narrative or the uh norm that society or the norm that mental health industry

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actually implements. So what is pain? Well, most of the times when we talk about pain, we are trying to concentrate on measurable quantities of pain. That is physical, mental, sometimes emotional. But there are several variations of pain. We have the physical, emotional, social, spiritual, cognitive. There are several versions of it. So it is harder to say what is pain. But more important to say what gets categorized as pain in our brain because well like we had seen earlier with the senses there are

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different types of these there are different ways in which it can be perceived. So if there is a stimuli at what point does it become painful? That is a much more interesting question to answer as opposed to saying what is pain. So the stimuli that often gets categorized as painful or understood as painful by our brain is something that we call as noception. The stimuli is a noxious stimuli. If you are hurt in your knee um and it creates a response that is well your pain responses are very high then it is

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termed as a noxious stimuli. If let's say someone doesn't if someone is using tickling uh in your um play behaviors at that particular point some for some people it can be just considered as plague for others just that tickling itself is extremely painful. In fact, as recent as a few years ago, someone did a study on heartbreak and looking at what are the pain areas in your brain that actually got triggered because of a heartbreak. And it is the similar kind of areas in the brain that were

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triggered if you had a heart attack. So how now those are completely two different things. So why is a heartbreak triggering the same areas of the brain as a heart attack? All of these things depend on the stimulus thermometer that we keep. It is all based on past experiences and how our brain has been architected in order to handle stimuli and the variance with which we actually end up interacting with these stimuli which brings me to the pain pathway. There are two different pathways when we talk about pain. We talk about the

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ascending pathway that is let's say if your foot is near the fire uh well the heat stimulus will end up traveling up your spinal cord and to your brain that is the ascending pathway. This is basically for your brain to make sense of whether or not uh putting your feet next to the fire is a good thing or not. Well, if it is not considered as a good thing by the brain, then the brain is going to go down the descending pathway and send a stimuli which will cause you to jerk your foot away from the fire.

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Now, that's a very simplistic manner of explaining. I get that. But what if we zoom in and see what's going on? Let's take another example. If you can bear with me and look to your left. Let's say we have a right hand and someone has punctured themselves with a nail on the right hand. What we do have are some sensory nerve fibers that go through this pathway which is the dorsal horn of the spinal cord and innervate in this area. when they innovate they release something called a substance P

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which is a neurotransmitter for this particular example. This substance P gets caught up by the second order neuron and it travels all the way up the spinal cord goes through your medula bones, your midbrain and ends up in your phalamus and inner weights over there which after that you get a third order neuron and that goes to your homunculus where you actually recognize the pain. So until and unless it reaches this homunculus, you do not recognize the pain. Irrespective of whether or not it is an extremely harmful, painful

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stimuli, you won't recognize it until and unless it has the information has reached the homunculus. This is your ascending pathway of the bra uh of pain for you to make sense of pain for you to perceive the pain. That is the reason why we have something called as the ascending pathway. But what happens after that there is always something uh that the brain has to do in order to deal with the pain and that is your descending pathway from your periquidal gray matter from your midbrain all the way down to the same

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area that the first neuron innovated. uh this is your descending pathway and it has a very important role to play. Let's zoom in into that room. All right, this particular area is what we call as substantial gel gelatinosa. [clears throat] We had the first order neuron that is in yellow. We have the second order neuron that is in orange. And we have the descending neuron over here that is in red. Now there's something very important happening here. Let's say the first order neuron that picked up your

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stimulus of pain came in into this area and released a neurotransmitter called as substance P. Now that substance P stimulates the second neuron which all the way goes up your spinal cord to your brain and well the brain ends up perceiving what that pain is all about. Until and unless your second order neuron is triggered your brain is not going to receive the information. So this step is extremely important for your brain to receive the information about pain. Your descending neuron that we see over here in red that

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came all the way down and innovated in the same area is the neuron responsible for well triggering an inter neuron to release opioids to release endockinabonoids all these interesting fascinating substances that our brain loves like anything. So this particular neuron is extremely important in order to ensure that you get these feelgood hormones. I wouldn't say hormones, I would say well neurotransmitters. So your endogenous opioid in this particular uh example is enke. What does enke do? It

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ends up ensuring that your first neuron and the second neuron no longer send the signal up the brain. So what happens when the signal is not sent up the brain? It doesn't process the pain. There is no perception of the pain. You don't feel the pain. This is the area in which uh many of the people who are in the field of BDSM will know of the TENS unit TE NS unit wherein you attach it you attach the electrodes to certain areas of your body and it releases electrical impulses and that's

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one of the many many ways in which you can avoid taking drugs and decreases and ends up decreasing your pain. uh perception. So you feel really good. It is also one of the mechanisms by which your violet wands and your aerotic uh electrostimulation devices are actually using and that is going to be something that I'll be covering in my next presentation because it goes into much more detail. Is there any questions about this? Which brings me to the most important part, the perception of pain. There are

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at least around four steps that we expect in order for pain to be perceived. And there are basically you have a stimulus. It goes through a perception. There is a sensation and there is finally an expectation of what the pain is supposed to look like and which informs again your perception of the stimulus. For this particular purpose I will be using um an experiment that was done if I'm not wrong let's see uh in 2016 in Italy. So in 2016 in Italy, what they did was they took uh people and they uh they shown a laser on

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the back of the hand and it was one of those uh lower end lasers but enough to probably cause some amount of pain but not that much that is extremely harmful for the person. So they were trying to look at whether or not or rather how much of pain an individual perceives to what duration and at what point even after removing the laser do they still perceive pain or do they not perceive pain. So what is the lasting effects of these things? Um so these individuals uh shown laser on the person's hand and at

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some given time point they well they switched off the laser and or rather it's kind of fuzzy the experiment here uh or rather the button was not really working. So there are two options in this particular case study. Um in the one case study uh we had uh the person who was pressing the red or rather clicking the red button in order to switch off the laser. So they will be given laser treatment for about uh five minutes or so and then it will go off and then laser treatment again and then 5 minutes and it will go off again. Uh

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after a while this individual ended up getting used to the laser. They got used to the pain. They started having an expectation of what the pain is going to look like. They got so used to it that at this particular time point wherein the red button was no longer functioning despite the fact that the person had actually switched off the laser. the laser was still on and the person had already perceived an amount of pain in the head that even though that the laser was still on, they did not flinch away.

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The laser was on for a longer duration than expected before and they were able to stand there with their hand underneath the laser for a longer duration. This completely stumped the people, completely stumped the researchers. It is an ethics violation. A lot of things that are associated with this particular research. At the same time, the question was why did the person not flinch? Why did they not remove the hand from the laser? Why did they continue to stand there under the laser for so long and not feel

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pain? They got used to the pain. What happens in the brain is that much of our processes is already pre-planned. Much of the things that we are going to do is already decided upon. There is already an expectation of what is it going to look like. So when there is an expectation of what the pain is supposed to look like and let's say you then introduce a stimulus if the stimulus meets the expectation then your prediction error is going to be zero. If the stimulus is lower than the expectation then there is a higher

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prediction error. If the stimulus is higher than the prediction error, there is also a higher uh if the stimulus is also if it is higher than the prediction that is there's a higher prediction error as well. It depends on whether or not the prediction error is positive or negative. I'll give you another example over here. Let's say you're going uh for um let's suppose you're going on a picnic with the garden. Now the last thing that you would expect in the picnic in the garden

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or rather the last thing that you would plan for is a bee coming in and stinging you. Now that is not something that your brain has predicted. That is not something that you have created a pain uh predictive coding in your brain that oh this is how much of pain this is going to have as an impact in my mind. No. So what happens is there's a higher prediction error here because when you subtract your incoming pain intensity with your expecting expected pain intensity there is a much much much

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higher pain prediction error. So the amount of pain you feel is going to be much much much much much higher because of this error. It all boils down to just that one teeny tiny thing. And it's not just with respect to pain. It's also with respect to pleasure. It is also with respect to uh so many things like oh how much of uh stress do you think this particular activity is going to um have me go through? Every single part of your brain has this prediction error and that's how it has

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been working. There is no way in which a brain can respond in 3 seconds or even lower than 3 seconds to a particular stimuli. This is the only manner in which the brain has evolved to do so. We go on taking stimuli. We all store it in our mind. We all store it in our memories in such a manner in which it can be retrieved at any given time point. And when it is retrieved, whatever stimuli that comes in [clears throat] later on gets measured against the stimuli to see if we are along the same track or not. I see a

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comment uh that explains why my kid is insistent that warm water is burning hot. Yes, indeed indeed. Yes. And and this speaks a lot more to how we introduce um pain even in our BDSM scenes. A lot of people would insist on introducing it in smaller quantities. in for shorter durations so that you can build up the pain pain tolerance. Why do we say that we are building up the pain tolerance is because we are creating a perception of what the pain is going to look like and eventually we get to a stage where

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we like oh yeah this is not that bad and you end up increasing your pain tolerance over the time. But there is this other aspect of this as well. If you remember that the descending pathway of the brain involves opiates, involves endockinabonoids. So perhaps at this particular time point is important to also uh suggest to the idea that the amount of pain you experience is dependent on how high your prediction error is. So if the amount of uh if the prediction error is high, the amount of pain you

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experience is high, then perhaps and I'm saying perhaps here, perhaps the amount of endockinabonoids and the endo opiates that you release is also going to be high, which results in you experiencing pleasure. Go go go go go go back to the last thing that you said. >> If I understand if the expectation increase is is high then the reaction or the sensation of it would also be high but that sensation is still pain but you said pleasure. So where's the transformation of that hurts into that feels good?

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Got it. Seemed like a big deal. >> So, got it. So, there are there are three um I would say three units that we are measuring. We are measuring expectation. We are measuring how much is the incoming stimuli and we are measuring what is the error between the two. Okay. If your expectation is high, your incoming stimula is low, then it is not really meeting up the expectations. So your pain is still going to be low. The prediction is high, yes, but your pain that you're experiencing is low. So it's not going to be salient

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enough for your brain to be like, "Oh, this is interesting. This is different. Is so different that I need to make changes in my brain." No. The only time that the brain does that is if it throws off the prediction completely. So if your prediction is low, your incoming stimuli is high then your and your pain uh prediction error is also high because of that subtraction. Then the brain is like oh I made a mistake. I did not predict well. And that is not a good survival stance for the brain.

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The only reason that the brain ends up predicting these things is order to ensure that it can survive in the future. So it has to ensure that either the prediction is exactly the same or it is a little bit higher so that you can still be able to survive. Now where does the pleasure come in is the question. Right? So let's say if your uh prediction does not meet your incoming pain intensity. So there is a pain prediction error that has been created. Now let's say that the incoming pain intensity is much higher

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than the expected pain or the prediction. At that point it may have an impact on your pleasure systems wherein you are releasing more opiates, you are releasing more endocin canabonoids in those areas in order to suppress the perception of the pain. So how do you perceive pain? You end up perceiving pain in the brain. After all of those processes goes through those uh neuronal tracts, you end up perceiving pain in the brain. When you end up perceiving pain in the brain several times, you create a prediction on

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various stimuli that results in a perception. When we calculate pain prediction error, we use the formula incoming pain intensity minus the expected pain intensity. Here expected pain intensity is also in reference to prediction. If your pain predictive error is higher than the expected pain intensity or if your pain prediction error is positive instead of negative then you are going to get a higher pain perception. So let's look into this further. Okay. So we have perceived pain minus predictive pain gives you pain

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prediction error but that is PPE. So if your PPE is greater than your expectation or your prediction then your pain perception is higher. If your incoming pain is greater than your expected pain then your PPP is higher. If your PPP is higher then your pain prediction is higher. If in general [clears throat] if your answer is a positive answer PPP equals a positive result then you have more pain. This forces the brain to learn. So pain is a signal that allows your brain to slightly rewire itself in such a way

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that it can learn from the scenarios that it is in. You see the brain is exists in order to keep the body alive in order to make uh make life better for your body in most circumstances. So if the brain has ended up in a situation that it has not predicted the outcome perfectly [clears throat] the way it was designed to do so then the brain has a lot more learning to do otherwise this individual may not be able to survive in this in this world that the brain belongs in. So what does the brain do? The higher

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the pain, the more the brain is inclined to rewire its connections to improve its pain predictions in order to ensure that this person survives. So in the similarly if your pain prediction error is in the negative that is you've experienced less pain then the brain is going to release pain relievers like endorphins uh and it's going to probably rewire in order to ensure that the prediction is better. But if the pain prediction is zero then you're not going to get any spike in activity in the brain. The

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brain doesn't want to waste any energy. Energy is a limited resource. So it doesn't want to waste any energy by taking any action. So let's look into this further. Let's say your incoming or your actual pain is about rated at four out of 10, but your brain has predicted it to be six. So when you subtract these two, you get a negative PPE. That means that the expected is higher than what your actual pain was supposed to be. In in this case, you're not you're going to have some pain relievers that's going

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to come in and the brain is going to improve its uh predictive abilities. However, if your actual pain is about eight and your expected pain is about what? Four, then your PPE is going to be positive four. Since it's a resulted in a positive response, you're going to experience a lot more pain than the other scenarios. This forces your brain to better predict situations. If your actual uh prediction is six, if your actual pain is six and your prediction is also six, it's going to result in a

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zero. So there is no spike in activity and the brain is not going to waste any energy by taking any action. Does this make sense? >> Yes. Yes, it does. Thank you. Another thing to note here is that I have not taken time into consideration. Now time is uh I would say it is harder for researchers to account for but there is some research that is happening right now where in uh cognitive neuroscientists are looking into temporal statistics learning uh to look at what happens to the pain in uh

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intensity over time. That is to say in chronic pain situations will it hurt less or will it hurt more? uh my hypothesis is that your uh baseline is going to be very very high but because you have already experienced it for quite a long time in your life and that becomes the new normal. So if that becomes the new normal, then it requires a lot more pain than your baseline pain in order for it to be triggered and in order for your brain to recognize it as oh my god, I'm having a painful stimula

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uh stimuli right now. To learn more about this research, you can always look into uh Flavia uh Manchini who is a researcher at University of Cambridge who is doing uh headed this research into uh temporal uh stimuli and how pain can uh how pain perception varies over time. One we have already gone through is that amygdala is a novelty and relevance detector heavily influenced by your past experiences. You will always see anterior singulate cortex also come up in these kind of conversations. This is to check for emotional and

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social context processing. Everything is context dependent. It works only for you in a specific environment. it cannot be applicable for every single individual. Insula is also another area of the brain that pops up. Uh this is this kind of again for those who have seen my lectures on uh neuroscience of disgust discrimination and dehumanization have actually seen this already wherein insula is the one thing that pops up all the time in order to say us versus them. we are our group and this is the out group. This is the in

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group. So that is the pro uh area that is talking about your internal body state and there's a distinction between me and you. Prefrontal cortex is also present in some cases but this is an extremely complex network system that requires a lot of uh energy to run. So in some situations that are highly triggering in nature, you will see the prefrontal cortex being shut down and you will only see amygdala functioning at that point. Why? Because amydala can make quick decisions. Whereas prefrontal

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cortex will always try to reason whether or not it is right or wrong, whether or not this decision making process is compliant with the rest of them. Another thing to note here is that prefrontal cortex will be developing up until you are 32. So for many of us prefrontal cortex has still not completed its development. It is required to take this long to develop. Why? Because you need to learn the hypocrisies of the world. Why is it that in some cases some people end up killing other people and then they are

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being labeled as killers whereas in some cases they have been given a medal and a promotion into the army. So it's the same job but context varies and the way in which our hypocrisies and the way in which we deal with our society also varies. So that all that processing all that complex uh behavioral systems come from the prefrontal cortex. Sometimes we may also see temporal loes coming in which are also responsible for memory and learning which brings me to the pleasure part of the uh class. Um I have a few questions

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here and indulge me so that I can address uh your learning needs. Uh what would you say dopamine if if someone says dopamine is a pleasure hormone is that true or false? We have one that says false. What do you think? Someone says true. So it's Two votes for dopamine as a pleasure hormone. One vote as dopamine is not a pleasure hormone. Well, it is not. Dopamine is also not a pleasure hormone. Let's try again something else. Testosterone does not cause aggression. True or false? We have a lot of people saying true and

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that's right. Testosterone does not cause aggression. Pherommones are like love potions. They make someone crave the other person. True or false? We have one false. And we have two false and two truths. It is false. Stress is good for your body. True or false? We have one that says depends We have a true and we have a false. So we have all the three in the spectrum. We have another true. Uh well yes it depends. So let's dive into each one of them. Let's first look into stress because we

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just addressed that. Now when we talk about stress, if you remember uh we are talking about stimulation. We're talking about when you stimulate someone at what given time point, how much of cortisol is released and why is the cortisol even released? So when we talk about stress, it is when we define it, it's basically a difference in environmental, physical, psychological factors that end up challenging your equilibrium or rather your understanding of your space, your environment, or rather your

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body's understanding of your internal environment. All of these things can cause stress. The myth is that the cortisol is bad for you. Why is that? Because when we look at the graph, we have an inverted curve when it comes to cortisol being released. That is to state that if you do not hit the at least the threshold level of uh stimulation, the per person is not going to um create that optimum state of functioning. So you need some amount of stimulation. You need some amount of cortisol to reach that optimum state in which you

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can actually function. If you don't, you're bored. If you don't, you're depressed. If you don't, you're sad. Now the point is it it depends in where on this particular graph you are at up until the optimum stage it is good it's perfect you have a great immune system all of those things but the minute it gets beyond that you get extremely stressed that's when you start noticing some amount amount of cortisol being harmful to you. However, if you do end up doing if you

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end up graphing this with respect to let's say inflammation or an immune system response, let's say you uh let's say you replace stimulation with inflammation from the graph. So higher the cortisol, >> what happens to the inflammation? It goes down drastically. But if you have a medium amount or a moderate amount of cortisol, the inflammation is extremely high. Now given this information it also boils down to is the system considering the moderate amount of cortisol stressful or

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not. That is the important question. It is not that if you have moderate amounts of cortisol your inflammation is high. You know, it depends on whether or not the information in your system states that there is a drastic change in the environment and hence I'm stressed. Unless and until that happens, you don't really get an inflammatory response. This is about cortisol. Let's try testosterone and dopamine, two of my favorite hormones. Testosterone does not cause aggression. Testosterone only amplifies society

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learned aggression. Let me rephrase that. Testosterone only amplifies societyle learned behaviors that help you maintain your social status and your position in your society. If that society is one that prioritizes testosterone, that prioritizes aggression as the method to maintain the social order, then you are going to learn that aggression is important for you to maintain the social order and hence you will if when you release testosterone it will amplify that aggression. If that society prioritizes

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um I don't know how much of charity donations you give out as a method of maintaining your social order then the amount of testosterone that you release uh is going to amplify the amount that you're actually going to donate. It only amplifies whatever we learn as society important in order to maintain our stance or our social structure for example and they did this for I think chimpanzees if I'm not wrong uh they did not go to the alpha chimpanzeee they went and gave the beta chimpanzeee some testosterone

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so if you say that a chimpanzeee ends up you know aggravating ing and you know creating an in higher response of aggression. It's not really directed at the alpha chimpanzeee. It is directed at the ones lower than him. He becomes an He becomes intolerable for those chimpanzees. And this is his manner of well stating I am at this level. I am higher than you and he wants to show that. So that is testosterone. Let's look at dopamine. Dopamine is interesting. Dopamine is actually released in anticipation

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of the reward. It is not released when you experience pleasure or when you experience the reward. It is released prior in advance. If you remember the pain prediction error, we have a reward prediction error as well. Surprising, isn't it? In anticipation of something that we classify as reward, dopamine is released. And not all the time. It depends when it depends on what is the probability of you receiving the reward. If you receive the reward 50% of the time and this is for all the doms out

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there please make note of this uh because if you let's say if spanking is a reward for someone let's say if that is an activity that creates pleasure if that is a reward um if the reward rate that is how many times you actually provide that reward in a session is 50% of the time then your dopamine spikes drastically in anticipation of it. However, if you all the time give that particular reward, it's going to spike very very low. So if you see 100% reward rate, the dopamine spike is extremely

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real. If >> you think of phenomenon like edging, right? People who do that delayed gratification, does that mean they increase their dopamine or just delay it? Is there more dopamine release or is it just delay? >> I love that you asked that question because the next slide after this is about delayed gratification. So, if you don't mind, I'll be going into that after I explain the reward processing error. So that way we can tie it up perfectly to the processes in the brain. Uh but yes

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to answer your question in short yes uh I will go into it in detail in shortly. So if your reward rate is 100%. Your dopamine spike is lower than the time that your reward rate is 50%. If your reward rate is 70% is about somewhere in between. If let's say dopamine is not being released as well a pleasure hormone then why is it that our perfume industry sells a lot of perfumes because if they are trying to sell sex if they are trying to sell reward then maybe our dopamine is actually spiking. No it is

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spiking in anticipation of it. It does not mean that if you wear the perfume it well you're going to get a reward. And again to clarify here it only spikes if sex is something that you even consider as a reward in the first place. That is important to note here. Is this kind of sex something that you actually consider as a reward or not? And given that if you do wear perfumes in anticipation of that, you may be releasing the dopamine at that particular g given time point because you don't know when you're going to get

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sex or when you're going to get laid if you wear that perfume. So it is pretty much 50% of the time you may or may not. So these are common myths that we have circulating around us quite often these days. Let's go into uh concepts of uh pherommones. One of the first pheromone that was ever discovered was bombico. It was released by silkworm moths uh the females to indicate to the males that they were ready to mate. Uh, ferommones have a wide range of behaviors beyond just signaling you are ready to meet. They

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induce aggression or alarm. They advertise territorial boundaries. They have parent offspring bonding going on. Uh, you have social behaviors that are kept under check and a lot more than just those. Broadly we can classify ferommones into two categories that is the release pherommones and the prim ferommones. The release pherommones are like fast acting short-term uh pherommones which causes lot of behavioral changes. Uh whereas primar ferommones are longer lasting hormonalbased pherommones. uh the release of pherommones are work

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like repelling or attracting other animals and in this case in primop pherommones they work at a much slower pace and it's generally for behavior and development in situations wherein the pheromone is no longer released for situations that is going to be beneficial to the individual and is sort of released in scenarios where it can backfire. Uh for example, the prey finds out that a predator is advancing towards it and starts scurrying about or in the scenario for the army ants who left a chemical trail so that they can find

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their home uh uh find their way back home. uh it kind of attracted the uh brown snouted blind snake. So sometimes pherommones can attract predators and that can actually put you to risk even more. So in these situations wherein the pherommones backfire, we call these pherommones as chyromones. Um there's another example of this is u a [clears throat] particular spider by the name bolus spider has evolved to mimic the pherommones of a specific moth in order to lure the moth into its spider web so that it can actually eat

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the moth. So there are various ways in which pherommones actually work. But the one way that we have been taught that pherommones do work is that oh they elicit sexual desire and elicit this whole need of wanting the other person and that it's acting like a love potion. Well, not so much especially in the case of human beings. Pherommones do not exist in human anatomy at all. What we do have is a $3.2 billion industry that is the perfume industry selling us sex. Well, the idea of sex, not pherommones.

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So what do I mean by ferommones do not exist? There are several ways in which we can look at it. There is this organ that most animals have called as the vom nasal organ VN O. We also call it the Jacobson's organ. They are present in most of these animals that I've listed over here who just got a dose of good amount of odorants. Um in humans we do smell things. It's not that we don't smell, we do smell things. We do like certain scents. We do like having a preference for certain odorants. But we are or rather

00:50:36

our endocrine is not tied down to the concept of having these odorants. What do I mean by that? Every time you smell an odorin does not mean that you get hard, does not mean that you get wet. That doesn't happen. It takes a long time for and a lot of things and a lot of senses to create this particular arousal state in human beings and it's just not oh you smell this you're already horny. It may be so for some individuals if odorants rank higher than the other sensory processes when it comes to

00:51:23

anticipating sex and when it comes to receiving sex as a reward and only in those individuals who have sex listed as a reward for them. So the whole thing that we are experiencing right now with ferommones is the even the idea of sex and whether or not that idea of sex is rewarding in nature. That is what the 3.2 billion dollar industry is based on not pherommones. So when we talk about pherommones, we are talking about receptors. We don't have the receptors in our nose. For some individuals, they may have the

00:52:10

receptor, but it can be dormant. That is to say, there is no connection between the receptor all the way to the brain. So if you remember, if you don't have a connection, if you don't have the neuron functioning properly, you do not perceive the stimulus in the brain. If you do not perceive the stimulus in the brain, that particular system is not working. Sometimes the neuron is not present. Sometimes the receptor is not functioning. Sometimes there are other issues down that pathway wherein it does

00:52:40

not latch on to anything and it does not result in a stimulus uh going to the brain. Either way, the romeronal organ is a vestigial organ that is present in human beings kind of like our um tailbone if it is present of course. So this is what what I mean by human beings cannot smell pherommones. That does not mean that we don't have a sensory gauge wherein we are like okay we like these kinds of smells but we don't like these kinds of smells. Uh we do have that we feel comfortable around certain types of

00:53:23

smells. We don't feel comfortable around the others. Uh some smells get us horny, some smells do not get us horny. And all of those things are there. They definitely exist. It's just that they're not pherommones. Why do I keep me mentioning that? Well, feromones have this capability of hijacking your system in order to get you ready for certain things like it could be uh getting ready for threat or getting ready to fight, getting ready to show aggression or uh it could be getting ready for sex. And all of that

00:54:01

is also mediated sometimes by your endocrine system. you release certain hormones and everything gets hijacked. Uh humans can function without it. There are a lot of people who are a noosmal. They don't smell at all and they are able to well get horny and have sex. They don't need a pherommon to tell them that okay now it is ready for you to have sex. No. Humans anyway have sex all the time irrespective of whether or not the whether or not the woman is actually in a situation wherein um she is ovulating. So we are not bound

00:54:47

by reproductive urges to have sex. Majority of the times when we talk about sex and ferommones we are talking about reproductive urges in order to have it. We are not bound by those things. But in animals they are definitely bound by it. Another thing that you will often see people mention is uh well we have a gene for this and we have a gene for that that means it is expressed. No just because you have a gene does not mean it's going to get expressed. The gene requires a specific environment for

00:55:26

it to express itself and for it to make proteins. Unless and until those environments exist, the gene is not going to express itself. And that is a whole other lecture on epigenetics and trauma and all of that that we are not going to delve into today. So every time you hear someone say, "Oh, we have a gene that means we are capable of doing this." No, does not mean that. It just means that there might be a 20 to 30% chance of you maybe expressing something like that. That's it. just 20 to 30%.

00:56:01

Everything else is dependent on your environment. It could depend on your internal environment. It could depend on your external environment. It could depend on prenatal environment environment that you were exposed to when you were developing in the womb. Or it could be even your family's environment that they were exposed to when they were alive up until the point that they made you. So anytime we have this conversation about gene, we have evolved far away from genetic determinism. That is to say, just because having a

00:56:37

gene does not mean there is a behavior does not mean certain traits are going to be visible, especially in human beings. We are not dictated by biological rules. We have evolved further off from that scape. So this is a flemen response on your right when your animals make that face. Let's just say they have perceived some pherommones and it causes them to freeze up and it's not a disgust response from your cat. Sorry, it is just the cat is getting a good dose of odors around it. Quite often with respect to pherommones,

00:57:19

you will see some odd here and there papers that might mention the word amygdala. And you might be wondering why is amygdala being referenced especially in the space wherein we are talking about pherommones. We are not talking about the fear. We are not talking about the fear center. So why is amydala popping up over here? And this was a paper that came out in 2009 that made a lot of headlines. That is to say, oh, we found the human alarm pheromone and we were able to identify it and all of that. So what

00:57:58

they did was they had some group of men and yes all of these papers are very hetroisetronormative kind of papers. You will see that throughout the literature. It is very very binary coded all the time which is annoying and the degree to which they want to maintain the binary coded language is also crazy. Um so yeah this particular paper well they had a group of sis head men u run on a treadmill wearing a few t-shirts and they collected those t-shirts and put them in a ziploc bag. Then they had a group of

00:58:41

other sis head men skydiving and then they collected those t-shirts and they put them in the bag and then they gave all these bags to a group of uh cishat women in order to say okay smell these papers uh I mean sorry smell these uh t-shirts and uh let me know if and basically put them under an fmri to see if there is any part of the brain that is being triggered when they are smelling these t-shirts. And lo and behold, the amygdala lights up and they're like, and it lights up for a specific particular t-shirt. And every

00:59:23

time they were smelling the skydiving t-shirt, the amigdula was lighting up. So they like, oh, a lot more uh sweat was released when the person was skydiving. They were extremely scared. And um that particular pheromone that was released in that sweat, the women were able to identify it and they were able to uh signal to the brain that something alarming is going on and hence they called it the alarm pheromone and well that became part of history right now. Uh media conclusion was we can smell fear that means we have fear or

01:00:04

alarm pharaohs. What went wrong in the whole paper was the fact that the amygdala is not a fear center. It does not light up only in response to fear. That is to say amydala is a novelty processing station. Any stimulation that is being brought to the brain if it is something different than the norm that you have ex that you have experienced up until now is going to have an amygdala reaction. Why? Because the amygdala is trying to check if this is relevant or not. Is this important or not? So it is a relevance and an

01:00:52

importance detector. It is detecting whether this is a stimulus that is salient enough. Uh and if it is stay salient enough, it's then going to process it as whether is it a threat or is it not a threat. Either way, there is some amount of information that is being coded based on this new stimulus. Why? Because your brain remember it is trying its level best to predict things all the time. And the only way it can predict things is if it is able to rely on already existing memories that it has created. In this

01:01:31

case, perhaps people the women had already smelled so many t-shirts full of sweat when they were uh running on a treadmill. So maybe that's not a smell that is unique. Maybe the smell that was unique was perhaps the skydiving uh sweat smell which is not something that every individual is going to be uh experienced around all the time. So maybe that elicited a response on the amygdala in a manner in which the amygdala is like oh is this a salient stimulus? It is a salient stimulus. It is a new stimulus. What do I do? It's a

01:02:12

novelty. Is it a threat? Not really. So it generates a neutral or a positive or a negative response based on how the amygdala is coding for it. There was this very famous 1994 t-shirt sniffing experiment that uh you wear the t-shirt for like 48 hours and uh you bundle up the t-shirts into a ziploc bag and give it to a group of women. They're going to sniff out the t-shirt that they are going to find as attractive. And this particular experiment suggested that they sniffed out the t-shirts and

01:02:53

the men with different immune system genetics are the ones that the women were actually attracted to. So the more your immune system is different from the women, uh women can get attracted to you. And this was one of the most famous papers that are still quoted even today in order to suggest to the fact that we have a pherommonal system. But it was debunked several times. Uh this particular paper was a very smallcale study wherein only 49 women were taken in and about 44 men were taken in all of them within the age

01:03:34

group of 24 to 25. um it has failed several replication studies especially when you create a large scale uh large scale study. Um this study was also recruiting only German students that were present in a particular university or something like that. Even later studies that came out of this uh were all very smallcale studies like there's this one study that came out suggesting that contraceptive use uh when women are actually using contraceptives then u they prefer men of the similar uh immune system which was exactly the

01:04:22

opposite of what this earlier study had suggested. So the conclusion was that contraceptives just change the whole narrative uh and flip it just the opposite. Even in this study you had only a UK study and the uh recruitment was only from the Newcastle University. It was a 2008 study where in 85 to 90% of the population were actually white. So you cannot really be applying the statistic for every single person in the world and there is a term for that. We call it weird data. So the reason why we call it weird data

01:05:07

is weird stands for western educated industrial rich democratic data. Predominantly this weird sampling represents um a white demographic which is approximately only 12% of the world. So we cannot be applying universality to these kind of studies because cultures are different and mating systems are extremely different across cultures. Uh most of the time it is actually determined by how close you are to the what is your proximity to the other person. How what close living quarters you're living in? Are you of the same

01:05:50

culture? Are you visiting similar uh spaces? Um do you go jogging around the same time? Do you end up in clubs at the same time? and you just end up part of the same culture or the demographic and then that's you're meeting pro mating groups basically but it cannot be applicable universally through the whole population so majority of the studies that you see that I'm going to bring up today are going to be studies that are extremely weird in nature also to note here most of these studies are

01:06:28

correlational studies they will be experimenting with something else and it will be correlated to some other phenomenon. That does not mean that there is a causal link between the two. Just because someone has sniffed a t-shirt uh and that person happened to be of a different immune system as that someone does not mean that there is a a equals b kind of a situation over here. Uh so we don't have any biological essentialism going on here wherein to say that uh because you're of a different immune

01:07:07

system you're going to attract somebody else of the different immune system it does not work that way until you actually see data that can suggest to the causal links. So here is another study that came out very recently that suggested to the fact that a majority of the research that is done today is 94.6% of white participants uh black Americans are about 2.5%. uh we have non-white participants which are like 0.5 uh e your Asian participants are like about less than 1%. So this is every single behavioral study

01:08:01

every single psychological study and social sciences study that we are seeing out there specifically with related to human behavior. This paper speaks to how much of the demographic is actually representative of the world and it's a very very small percentage. So we have reached a stage now where in many of the researchers feel that this field of human pherommones are so controversial and so sensational at this point that they're like let's just scrap everything and start from the scratch.

01:08:43

It's kind of like saying we are going to study uh meditation and if meditation helps or not and whether it helps or not is going to be very difficult for someone to actually design that study because there is no control subjects. Uh you generally need to have a control and an experimental group in order to design studies. You can never have a control uh in a meditation based study because they are not going to be blinded. That is to say that everybody is going to have a bias at the end of the day. It's even

01:09:24

the researchers as well as the participants are going to have a bias. We can also have a lot of placeos that might come in into the picture and playing a lot more role than we require them to do so. And that's also being the fact that none of these studies are going to be double blind studies. They're not going to be easily replicable. They're not going to be large scale. They're going to be extremely small scale studies. So hence they cannot be applicable for the whole generalized population of the world.

01:09:56

They can only be applicable to just that small group of 44 students that were recruited from that university. That's it. it cannot be applied for anybody else beyond that group. So let's finally go into dopamine pathways and I know we have very little time so I'm going to quickly go through these. We have around four different pathways when we talk about dopamineergic pathways. It's the misolyicquat pathway, misoccortical pathway, nigrostyal pathway and tubroinfendubular pathway. I will never get that in my

01:10:40

life. Either way, dopamine seems to constantly be produced in these areas like the vententral tagmental area that's the VTA and the substantial Both of these are very very rich in dopamine uh or dopamineergic neurons. Fun fact, VTA vententral tagmental area is also lit up when you are uh snotting cocaine. And guess what? VTA is also lit up when you are experiencing something like a new romantic relationship. So any NREs that you are experiencing your vententral tagmental area is going to light up. So the

01:11:25

similar pathways that are involved in cocaine were involved in new relationships as well. So when we talk about dopamine and that's the paper on the right. you can always uh scan the QR code and it will give you the access to the paper. Uh remember when I mentioned the 50%, 70% and 100%. So let's say you were provided with a stimulus and that's the signal that goes in over here and that stimulus let's say let's look at something like a BDSM terminology here. Okay, let's say

01:12:10

if the dom comes up to you and says uh or rather you you are known that um 100% of the time if you're doing a particular task you're going to be spanked and let's say spanking is something that's going to give you a reward not really something that is a punishment so it's pleasurable for you then your spike rate is going to be what is shown in 100% over here in red. That is the maximum level of dopamine you are going to release prior to receiving the spanking. So before you receive the spanking, your

01:12:53

brain has already released this much of dopamine. Let's say if your reward rate or the amount of time that you're going to get spanked is only like 70% of the time, then you're going to get a slightly more uh amount of dopamine that is going to be released. That's in yellow over here. But let's say you cannot predict it or let's say your spanking rates are going to be 15 50% of the time you're going to get spanked and 50% of the time you're not going to get spanked. your dopamine rates are going

01:13:28

to be extremely high in comparison to the others as well. And there and this only works in situations if spanking is your preferred mode of pleasured driven stimuli. Uh this can work in several ways. Uh [clears throat] if you have a sweet tooth, if you're doing a particular task, uh every time you do a task, if you are going to get a cookie, then you by now your brain has already figured out that every time you do this task, you're going to get a cookie. So it's going to release only that much of

01:14:06

dopamine that is shown in the 100% reward rate. If let's say 70% of the time you're going to get a cookie, then your reward rate is going to be what is shown in yellow. But if you're going to get a cookie 50% of the time, then your reward rate is going to uh then your dopamine levels are going to be much higher than that. And remember all of this is going to be much much in advance of you actually getting the reward. And if you notice here in the graph, it is also in advance of you actually doing

01:14:41

the work. So after a point, it's going to get that before you are doing the task, you are already signaling a dopamine level, which brings us to pleasure prediction and reward prediction errors. So like we had the pain prediction errors, we also have a reward prediction error. So if your actual reward uh rate is about 50% of the time and your predicted reward rate is about 100% of the time, then you result in a negative reward prediction error. Then your dopamine levels is going to drop below baseline. However,

01:15:31

if your actual uh reward rate is about 100% of the time and your predicted levels is also about 100% of the time, there is no phasic drop in dopamine. If your actual is 100% of the time, if your predicted is about 50% of the time, then your reward prediction error is extremely high, it is in the positive. So, if we are able to apply this to certain scenarios. So, let's say scenario one. You walk in into a coffee shop and you get a $4 tasting coffee and you take a sip and it's an exceptional

01:16:08

coffee. It's an award-winning roast coffee and it is worth uh worth about $7 and you're wondering why did I pay you just $4? What happens to your dopamine levels at this point? Well, when you calculate it, it becomes 7 - 4. you get an uh positive uh reward prediction error. And because you have received a pro positive reward prediction error, it reinforces this whole behavior to return to that coffee shop because you have had a release of dopamine at that point. The same thing if we pick up scenario

01:16:50

number two. You buy a cake of slice and uh you value it at around $10 and you take a bite and it's completely stale and bland and it's worth only $2. What happens to your dopamine level at this point? It is 2 - 10. It is in the negative. It is -8. And since it's a negative prediction error, your dopamine self firing drops below the baseline and signals your brain to lower its expectation or avoid buying that cake again. And the same thing if let's say you and your partner are in a long-term

01:17:32

relationship and you have had very comfortable and a familiar routine. Every Friday you end up having sex. It's in the same position. minutes in the same bed. You have created a reliable expectation of how sex would make you feel and how you will experience what and what you will experience and you rate that experience as 6 out of 10. What happens to your dopamine levels? So since it your expectations have been met, it's 6 - 6 it's zero and you don't get any reaction in the brain. There is no

01:18:09

need to waste any energy of the brain because the brain has predicted exactly what is going to happen. When we talk about delayed gratification, this particular reward rate is completely unpredictable. You don't know when it's going to happen. It completely overrides this whole process of reward processing error and prediction and actual and what amount of dopamine is released. You don't know. You don't know. So what happens? It is always by reward processing error because you're unable

01:18:45

to well predict. So your dopamine is going to be high. And this huge spike in dopamine in anticipation of the reward, it increases the subjective value of waiting itself. And that creates that high motivation to even wait. This is edging. This is what delayed gratification looks like in the brain. This is the last part of the lecture today wherein I am going to ask you one more question. Can humans feel wet? Yes or no? Or in this case, humans can feel wet. True or false? The answer is no. And that's right.

01:19:42

Humans cannot feel wet. Humans have thermo receptors. They have mechano receptors. So they have receptors like uh you can feel temperature. So if it is cold, you generally think it is wet. It's like putting a pulling out a towel from the dryer. And if you feel like it is cold and you end up actually perceiving it as wet, it might just be cold. But this is what I mean by your brain trying its level best to ensure that it is predicting scenarios that is present. In this case, it talks about uh

01:20:25

receptors per se. So majority of the times we just perceive changes in systems. We don't perceive uh wetness per se. There are specific receptors for that which animals do have uh but we do not have those receptors. There are several different types of receptors. U the ones that I'm concerned about right now is through the functional classification over here which refer to photo receptors, thermos receptors, mechano receptors, chem cheoceptors and noiceptors. Noceptors are the ones that

01:21:01

we had engaged with in our last lecture wherein we spoke of pain stimulus. It is the noceptors that are responsible for that. Chemo receptors are often resp uh involved in any um nervous system regulation or anything regarding hormonal systems you often have chemoceptors involved there. Thermos receptors and mechano receptors are the ones that we are generally going to deal with when we are talking about oh am I feeling wet down there. Well technically it is just thermal receptors or mechano receptors. Photo receptors are the ones

01:21:37

that we use for light based stimuli. A little bit more about mechano receptors per se. We have several of them like rafini ending. We have pansen uh pinian corposil. We have misnner corpusle. We have merkel's disc. We also have krauss corposals which is making a lot more uh uh news these days. Uh but let's look at how it works. Let's see a misnosal. Misnoposel contains a lot of these cellular bodies inside of it which when you nudge can actually move in a particular direction and when it moves

01:22:23

in a particular direction sodium ions flow into the corpus. And when sodium influx of sodium ions flow into the corpusel it creates a a situation wherein uh you can generate an action potential and that excites the particular nerve which results in uh the whole nervous system to be excited and you uh move the electrical charge down the nervous system. So even a small nudge can just result in the movement of these cellular bodies and then sodium ions flowing in which results in the nervous system being excited at the end.

01:23:10

But what does that look like when it comes to something like sex related topics? When we talk about vibrators or uh clitoris suction devices any of these things they work with grow corpusles. Uh similar to the previous case uh in this case we are going to be dealing with calcium ions as opposed to sodium ions. So when crosles are being triggered and crosles can detect anything from thermo uh from thermal changes like oh it's getting colder or not to small vibrational changes uh as well at the surface of the skin and upon

01:23:59

receiving such vibrations um calcium ions can calcium channels can open up and then the calcium ions can come in which results in the uh nervous system activation. Why? Because you have an action potential that is being generated which excites the nervous system. There is a very specific channel within the axon of the nervous of the uh neuron where we talk about piso 1 and piso 2 channels. Surprisingly, Fiso2 channels were developed for gustatory mobility. That is to say, when you're eating something, it has to

01:24:41

travel down the pipe. It has to move into the systems in and out of the systems. And all of that was handled by Piso 2 channels. They played a major role because they evolved to do that. Somehow very recently, this was the most recent paper that I have read which spoke about the same piso2 channels being involved in the movement of calcium 2 ions uh in such a way that it can result in uh action potential and can make you feel aroused. So, and I think that's all for today. And if you're all interested, I will be

01:25:27

sending this recording to you. Um, these are some starter resources that you can go through and crossverify and challenge anything that I have said that is completely wrong and that doesn't feel feel right or sit right with you. We are all here to learn. And if you'd like to touch base with me, here's a QR code, my website, and my email that you can always touch base with me and we can have this conversation again.