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I'm currently doing my postdoc in neuroscience and epigenetics (neuroepigenetics) at a major US medical school. I received my Ph.D. in Neuroscience in 2015, and altogether I've been working in academic science for over 10 years. My background is in the hypothalamus, and in particular the control of food intake, appetite, and energy expenditure. Parts of this brain region, through their connections with the autonomic nervous system, as well as peripheral signals of energy balance (hormones, nutrients, etc.,) play a major role in governing our food intake and body weight regulation. I also have a lot of experience studying the neurobiology of sex, drug addiction, stress, and mental illness. When I was in grad school I spent a fair bit of time teaching undergraduate classes, and one of the things I truly miss now that I'm spending all of my time in research is the range of questions I'd get from students. Apart from feeling like I was helping them learn, I'd inevitably learn a lot myself in trying to research answers for them. For this reason, I'm keeping my first post here very open-ended. While my specialty is food intake/energy balance/obesity and the brain, I'm pretty familiar with all the different areas in neuroscience at this point so I'd really love to try to answer your questions on anything in the field. This could include questions about neuroscience/academia as a career choice, the graduate student/postdoctoral lifestyle, and other such things, though there are plenty of specialized threads for that on these forums and in the SAL subforum. Anyway, I'm just giving this a shot, so please ask away and I'll try to give you the best researched answer I can!
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Jun 13, 2019 01:53
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I'm curious as to what your take on the promises that are made in the name of neuroscience as to practical applications for mental illness. I ask from the position of someone working on the other side; one has been hearing - from people who mostly are not themselves neuroscientists, mind you - that neuroscience is going to revolutionize everything we do and it's just around the corner. And it's been just about to come for about fifteen years, with no real change, but the promise is constantly made. And while it's interesting to know how the neurotransmitters in someone's head have been altered in response to this or that trauma or whatever else, that information seems, at least to me, to have no immediate application to the work one does with patients. Do you see that changing? Or more generally, what do you think about the state of the field versus how it gets hyped?
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Jun 13, 2019 04:46
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Numerical Anxiety posted:I'm curious as to what your take on the promises that are made in the name of neuroscience as to practical applications for mental illness. I ask from the position of someone working on the other side; one has been hearing - from people who mostly are not themselves neuroscientists, mind you - that neuroscience is going to revolutionize everything we do and it's just around the corner. And it's been just about to come for about fifteen years, with no real change, but the promise is constantly made. And while it's interesting to know how the neurotransmitters in someone's head have been altered in response to this or that trauma or whatever else, that information seems, at least to me, to have no immediate application to the work one does with patients. Do you see that changing? Or more generally, what do you think about the state of the field versus how it gets hyped? I'm not particularly bullish on the potential for neuroscience to revolutionize our treatment of mental illness in the near future. It's as you said, there have been no shortage of promises made over the years, but there's been very little in terms of progress. There are some exceptions, mind you, where rather surprising treatments like ketamine have shown promise in rapidly mitigating treatment-resistant depression. But for the most part, the drugs we have are very dated, and work in a way that doesn't have much to do with our current understanding of how mental illness manifests in the brain. Most neuroscientists would probably agree that long-term mental illness is not primarily a chemical imbalance but rather some kind of fundamental difference in how the brain is wired and organized. Imaging studies, and studies on post-mortem tissue seem to confirm that for many conditions (and this scales with the severity of the condition), there are real structural and functional differences in the brain. These structural and functional differences may overlap to some extent with brain regions targeted by particular neurotransmitter systems, and so drugs that modulate those neurotransmitters might have a beneficial effect. But I don't really think that they are doing much to correct those problems in the first place, and really what they're doing is probably more analogous to how you can temporarily relieve the pain of a bruise by rubbing the skin around it --- the nervous system reacts to counter-stimulation in interesting ways. I think neuroscientists and clinicians are more optimistic than me in this area though, and I think it's a pretty widely held belief that neuroscience is information poor but rich in techniques, and if we could only collect enough big datasets, we'd be able to put everything together and understand how the brain works. This optimism is rooted in the fact that we probably will require machine learning and high performance computing to stitch together such an understanding (after all, how can the brain understand itself in sufficient detail?), and computers are getting better every day. But there was a pretty famous paper a few years back that attempted to apply all of the techniques of computational neuroscience and connectomics to understanding how a simple microprocessor works (1). Since every structural and functional detail of the microprocessor was known to the researchers, they could readily assess how well the methods of neuroscience fared in figuring out how the chip worked. In the end the methods were able to pull out some trivial signals from the data, but didn't come anywhere near understanding it, even though they had literally every piece of data that was possible to collect. This tells me that even the best methods available to neuroscience now will probably not be able to figure out how the brain works, much less how mental illness perturbs its working. This, I think, is the reason for the growing fascination with psychedelics. If we allow that many mental illnesses are disorders of thought that are manifested in the structural and functional organization of the brain, maybe the best route to treatment is to do something that "turns of read-only mode" in the brain's wiring and makes some of its deeper workings more plastic and accessible to consciousness. Psychedelics seem to do this, and they might allow for a kind of directed re-shaping of thought patterns and, presumably, their associated neural pathways. I should note that this would not be a good approach for more severe conditions like schizophrenia, bpd, or anything like that. This is an area to watch. Ironically if it turns out to work in clinical trials, it would be an example of a therapy that doesn't need any neuroscientific knowledge whatsoever to apply --- it could be strictly the domain of psychologists and other experts in human thought. Anyway those are my thoughts. I had to resist getting into talking about obesity, because that's another area where we know the brain is involved and where we gain vast amounts of new information every year, yet find that any kind of pharmacological solution is perpetually out of reach. (1) blogged about here: https://www.theatlantic.com/science/archive/2016/06/can-neuroscience-understand-donkey-kong-let-alone-a-brain/485177/
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Jun 13, 2019 05:47
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so one question i have is pretty specific - that circadian clock that gets activated by tiny doses of methamphetamine even when you nuke the home of the primary clock, the suprachiasmatic nucleus; do we know where it is yet? apparently in 2013 we didn't. this is a way overspecific question, though and as a more general question, could you possibly explain how the brain processes smell? sight has some aspects that are understood from those weird cat torturer scientists, and it seems like it builds up an idea of what's happening from basic principles. is there any such underlying logic for smell, or is it just a mess of wiring we don't understand? or perhaps the truth is in the middle edit: and my understanding of sight is obviously limited too, i'm sure i would benefit from an explanation of that
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Jun 14, 2019 23:40
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I know I'm handing you a land mine here, but I'm always very curious about how sexually manifests through the lens of Neuroscience. I'm gay and have had suspicions about my own sexuality since I was about 12. The thing that finally convinced me of my own sexuality was actually boobs. Everyone talked about boobs and rear end, and I had no interest. High school me was too busy day dreaming about athletic muscle structure, and well-defined collar bones. I'm deeply interested in why this happens in an individual and the evolutionary components to it (gay Uncle, etc) as it seems so counterintuitive. Do you have any neat insights about weirdness in sexuality? For a fun version of this, I'd have the same questions about fetishes as well!
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Jun 15, 2019 02:50
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oystertoadfish posted:so one question i have is pretty specific - that circadian clock that gets activated by tiny doses of methamphetamine even when you nuke the home of the primary clock, the suprachiasmatic nucleus; do we know where it is yet? apparently in 2013 we didn't. this is a way overspecific question, though Ah yes the methamphetamine-sensitive circadian oscillator (MASCO). So this is an interesting case that's very analogous to something I have a bit more background in, which is the food-entrainable oscillator (FEO). Both of these are hypothetical systems within the brain that can govern circadian behavioural rhythms separately from the body's master clock in the suprachiasmatic nucleus (SCN). A bit of background for others reading Think about how most behavioural rhythms in animals (including us humans) are follow an approximately 24 hour period, and are governed primarily by the light-dark cycle. These rhythms exist even when you remove this light-dark cycle, either by blinding the animal or keeping it in constant light or darkness. Usually the period of their rhythm is not exactly 24h, so in the absence of a light cue (a zeitgeber, German for 'time giver', as it's called in the field), the daily pattern of behaviour will gradually shift with respect to the actual time, but it will still maintain its periodicity. In other words, animals in constant dark will still spend about half the day sleeping and half day awake, even if the "day" for them ends up being 24.5 hours instead of exactly 24. We normally think of light as the primary zeitgeber for animals, since circadian rhythms evolved in the context of the day/night cycle of our rotating planet, presumably to optimize behaviour and energy use for the time of day. This light-entrainable clock affects every bodily system, but is organized in a specific brain region called the suprachiasmatic nucleus (SCN) in the hypothalamus. Researchers have also found that food access and, surprisingly, methamphetamine administration, can also entrain behavioural rhythms that are very similar to the normal light-dark rhythms of the light-entrainable clock, but neurobiologically distinct. The question, then, is where are these other clocks located in the brain, and what is their purpose? Back to the question Finding the location of oscillators in the brain is quite challenging. One of the simplest ways to do it is to use some kind of marker of neural activity (expression of genes like c-fos, uptake of 2-DG, etc.,) and search through the entire brain in animals sampled at regular intervals over 24h. In my Ph.D. lab one of the students spent a lot of time doing this in search of the FEO and ultimately found some hints but nothing as unambiguous as the SCN is for light. The SCN, by the way, is a gift to experimenters because it's extremely anatomically localized, neurochemically distinct, and shows very clear rhythmic activity. Nothing comparable has been found for the FEO or the MASCO, but the dorsomedial hypothalamus (DMH) is presently a leading candidate for both. A paper from 2017 found that the clock gene Rev-Erba is pretty much the only canonical clock gene that's actually required for the MASCO to function, and mice that don't have this gene cannot maintain methamphetamine-induced period shifts in DMH neural activity. There's also a role for dopamine, because dopamine receptor antagonists can disable the MASCO, and there are also meth-induced rhythms seen in the striatum (a key target for dopamine signalling). Serotonin may be involved in inhibiting/masking the normal clock signals coming from the SCN as well. So in summary, no we don't know where it's located. My suspicion for both the FEO and MASCO is that they're distributed systems that don't reside in a single, anatomically distinct locus (again, we got very lucky with the SCN and how anatomically compartmentalized it is). Rhythms can emerge additively from a combination of non-rhythmic or out of phase processes (think of beat frequencies), so the normal method of looking at individual areas one at a time probably won't cut it anymore. I also suspect that they are probably just different manifestations of the same basic system, because it makes sense evolutionarily to have food-entrainable rhythms powered by dopamine, but methamphetamine-entrainable rhythms don't seem to have a place in evolution and may be a byproduct of a more useful process. oystertoadfish posted:
Those classic cat torture experiments turned out to be useful in providing a template for understanding all of the senses. Our language doesn't really make this intuitive, but many of the challenges in visual or auditory perception also apply to olfaction. For instance, vision research asks how the brain separates figure from ground, or how it distinguishes 'objects', even though viewing angle, background, lighting, distance, etc., can all have a huge effect on the actual image that reaches the retina. These same questions apply to olfaction, for example how can you separate the smell of an apple from the smell of the leaves on the tree? Or how is it that you can identify the smell of cinnamon rolls whether you're in a mall, outside, or in your car, each of which has a dramatically different set of background odours. The wiring of the olfactory system basically is a mess, and quite different from the other senses that follow a more circumscribed route from the sense organ to the cortex. But even though the olfactory wiring is messy and weird, we are beginning to see that it follows a similar logic to the other senses. That is, there is a great deal of 'top-down' processing where higher order brain regions project back down to lower sensory regions to modulate the signal they send. The whole system, in fact, seems to have a hierarchical organization that's quite reminiscent of the basic plan for the other senses. The piriform cortex, which is one of the many areas the olfactory bulb projects to, seems to be a key site for the integration of basic sensory input and higher-order cognitive processing. It's kinda analogous to the associative cortical areas downstream of the primary visual areas. The piriform cortex also seems essential in habituation to persistent background odours, suggesting that it plays a role in olfactory "attention". So it seems that olfaction is increasingly being seen as having properties analogous to the other senses. Even though it's evolutionarily much older, and anatomically quite different, it looks like the basic requirements are similar for all of the senses and thus they all seem to converge on similar neural processing mechanisms. We really don't know that much more about how it works, but I think the basic parameters of the question are better phrased these days so more and better neuroimaging can potentially make progress on this in humans. Rodents have many more olfactory receptors than us, and the problem is further complicated because they cannot verbally describe their experience.
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Jun 15, 2019 19:09
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Canine Blues Arooo posted:I know I'm handing you a land mine here, but I'm always very curious about how sexually manifests through the lens of Neuroscience. I think our discourse on sex and gender would be much healthier if everyone understood how sexual differentiation in the brain actually works. Male and female brains differ in a graded way - there are no binaries in the brain, but there are differences in the size and cell density of certain very specific parts. Our research on rodents shows that these differences are largely not a product of which sex chromosomes you have, but rather the level of sex hormones you're exposed to in the perinatal period. The first such brain region discovered in rats is called the sexually dimorphic nucleus of the preoptic area (SDN-POA), part of the hypothalamus. This region is about 5x larger in male rats than female rats, but you can reverse this difference by injecting newborn female rats with testosterone, or by castrating newborn male rats. In other words, the size of this brain region is quantitatively different between the sexes, and regulated by early-life sex hormone exposure. Rats treated this way also take on the sexual behaviours of the opposite sex. These are called organizational effects of hormones, and they are only possible during certain critical windows. The flip side are activational effects, the actions of hormones on mature systems (think of the menstrual cycle, for example). This basic principal also applies to other sexually different or dimorphic regions throughout the brain (there are a number, but we're not sure of the significance of most sex differences). What does this say about sexual orientation? Well it suggests that sexual orientation is driven in part by differences in brain structure, and that differences in brain structure are graded and often driven by organizational effects of hormones. Importantly, this does not suggest that sexual orientation affects adult hormone levels - there's no difference in testosterone levels between gay and straight men, for example. Is there any evidence for differences in sex hormone exposure for gay men compared to straight men? Possibly, but it's difficult to measure because these data are not typically collected in pregnant women or newborns. However Simon Levay famously found that the size of the 3rd interstitial nucleus of the anterior hypothalamus (INAH3), a region of the human brain analogous to the SDN-POA looks more 'feminine' in brains from homosexual men. This is an old observation, but it's been replicated several times and seems to hold up. Human sexual orientation is obviously much more complex than rats, and so the size of a single tiny brain region can't possibly explain everything. However this kind of discovery has the properties we'd like to see out of an explanation, namely that it's a hormonally-mediated, measurable difference in a sexual part of the brain that's established early in life and impossible to change afterwards. A lot of the modern work in this area is done by a Dutch researcher named Dick Swaab, which I find pretty funny. Another interesting effect is the fraternal birth order effect. The more male children a mom has, the higher likelihood that her sons will be gay. Something like 15-29% of the likelihood of being a gay man can be attributed to this effect (each older brother a male has increases his odds of being gay by about 33%!) This is probably the most robust and best documented biological contribution to sexual orientation (even more than genetics!). It seems to happen because moms begin to develop an immune reaction to a male-specific protein produced by the male fetus. This protein is expressed in the male fetal brain, and if mom's immune system starts to react to it, this could affect brain development. Sexual orientation is also genetic, though I don't think the exact genes or their mechanisms of action have been determined. I don't think there's any conflict between this fact and evolution. To begin with, there's no "gay gene", so even in individuals who happen to have a lot of 'gay alleles', it's not a 100% chance that they'll end up being gay. Again, sexual differentiation is a graded, hormonal process that does not result in clear binaries. The idea that gay alleles benefit individuals and families that possess them by positively influencing other behaviours, or allowing non-reproducing kin to contribute resources to child rearing seems to make sense to me. I hope that's interesting and/or helpful. I should point out that a major flaw in the way this research is framed, even in today's semi-enlightened age, is that homosexuality is still seen as an aberration to be explained, rather than a natural variation in human behaviour. In fact, all kinds of animals exhibit homosexual behaviours in the wild (and especially in captivity), and there's no real reason to think that it's not simply another dimension of human variation. We might just as well ask what 'causes' heterosexuality, but that's really not how the question is phrased. Culture inevitably influences how scientists ask questions, and we can't pretend that any of this is as objective as astronomy or whatever. Whatever the neural substrates of sexual orientation are, they make up an extremely tiny fraction of the overall brain. Potentially the minimum difference needed to determine whether an individual is primarily gay or straight could be just the size of a particular part of the hypothalamus, and to imagine the amount of pain and suffering visited on people for the sake of having a different number of hypothalamic neurons is incredible. I don't know much about fetishes or things like that, but there was a neat study done a few years back where the researcher made little jackets for female rats to wear, and then allowed naive males access to either plain or jacket-wearing females. Males who had their first sexual experience with a female wearing a jacket tended to prefer those kind of females in subsequent experiments. Taken at face value, it suggests that some fetishes may be result from unique life experiences. The basic nuts and bolts of sex and sexual orientation are handled in lower brain regions, but the finer points of attraction like integrating sensory cues and memories are handled in higher brain regions that are plastic and can be shaped by experience.
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Jun 15, 2019 19:52
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What’s your least favourite thing to explain to people about neuroscience/ the life of a neuroscientist? What’s the one thing you wish you could do more of in neuroscience, but the funding not allow?
johnners 2.0 fucked around with this message at 21:30 on Jun 15, 2019 |
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Jun 15, 2019 21:06
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johnners 2.0 posted:What’s your least favourite thing to explain to people about neuroscience/ the life of a neuroscientist? What’s the one thing you wish you could do more of in neuroscience, but the funding not allow? I think my least favourite things have to do with popular misconceptions. I feel obliged to argue with every anti-vaxxer, or anybody else with fringe opinions on how mental illness/brain problems should be treated. This also includes "grain brain" people and people with incorrect opinions on obesity (since that is my main area). I mean it's much easier to let these things go, but I feel like it's a cop out to let the science-engaged public fight all the battles for me. If anyone should be on the front lines of these debates, it ought to be the scientists. As for the life of a neuroscientist, I guess I'm tired of explaining to family how long/difficult the process of succeeding in academia is, the level of dedication it takes, and how common failure is. I've been reasonably successful in my career on the whole, but I'm still rejected for most grants and jobs I apply for, and my papers are always rejected the first few times I submit them until I find the right journal. It's just part of life and every rejection doesn't require a big re-think of my life choices or a pity party or whatever. A really simple thing I think that could improve neuroscience a lot, but is never done due to funding and ethical constraints is to run studies in multiple strains of mice. The most common variety of mouse used in this research (C57BL6) is a massively inbred freak of nature that would never survive in the wild. They have a lot of idiosyncratic behaviours and genetic abnormalities, and I think we're missing a lot by using them from 99% of studies. From time to time scientists will try to replicate experiments in other kinds of mice (or rats even), and find that they get completely different results. A lot of genetic mutations/manipulations, for example, only work in the context of the genetic 'background' of the C57 mouse. If you repeat the same genetic manipulation in a different kind of mouse, their genetics may have a way of compensating. So if we're trying to make conclusions about what a particular gene does, we really need to try it in multiple kinds of mice at the very least Consider the fact that even two different strains of mice are 99.99% genetically identical, and so if something works in one strain but not the other, what are the chances that it tells us anything meaningful about humans, a species that's genetically very different from mice? We're doing all of this work to try to find information about the brain and genetics relevant to humans, so we need to be sure that our conclusions are robust across multiple strains of mice at the very least if we hope to make cross-species comparisons. To do this would require several times more funding, since the same study would need to be repeated multiple times, and nobody is interested in paying for this. funny song about politics fucked around with this message at 00:33 on Jun 16, 2019 |
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Jun 16, 2019 00:31
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This is a fascinating thread and I'm really enjoying the level of detail and care you put into responses. If I have more questions, I'll definitely be back!
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Jun 16, 2019 00:52
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Really interesting thread so far, thanks for posting. I'm doing my undergrad honours right now, looking at whether ageing has an effect on neuroinflammation following a systemic reaction (basically we're injuring mice with a myotoxin then seeing if the inflammatory response leaks into the brain and whether old mice have a differing response to young ones.) We're mostly focusing on macrophages and microglia since the group's research focus is primarily immunoageing rather than anything to do with neuroscience, but I'd be interested to know more about the kinds of effects ageing has on the brain and whether you think the immune system has effects on how the brain functions day-to-day? I know what you mean about mice, seems like a lot of areas of bioscience have the same issue where effects are seen in C57 mice but it's a bit dubious how transferable that data is into people.
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Jun 16, 2019 03:05
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You mention appetite and hunger as one of your areas of study. As a Canadian experiencing legalized weed, and the munchies that is experienced, do you think there will ever be enough advancements that one could produce GMO weed to interact with our brains to eliminate this problem? Also, what do you feel is your most unethical thing you’ve done? What’s the dark underworld of neuroscience.
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Jun 16, 2019 16:11
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i want to thank you for the detail in your responses as well. i learned something about MASCO! circadian rhythms are so rad your comment about mice and ethics brings up an interesting point to me. i worked with circadian poo poo in undergrad and because the mice were in perpetual dark and such we had to care for them ourselves. i think that i felt weirder about killing them and injecting formaldehyde into their hearts because i'd had to feed them all the time and poo poo. how much interaction do you have with your test subjects and do you think it affects your feelings about medical ethics? or do you just do research on drosophila or w/e where you can throw a jar full of em into an autoclave and nobody cares to clarify the above: i'm asking for your thoughts on the thorny ethics question in general if you care to share them, but in specific i'm really just asking about how your personal opinions on medical ethics have been affected, or not affected, by the degree of contact you've had beforehand with the rodents in question i did make the 'cat torture scientists' comment a while ago, but i'm honestly undecided on this general set of ethics questions, so i'm not secretly trying to bait you into something or some poo poo
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Jun 17, 2019 00:06
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Any recommendations for pop neuroscience/brain stuff books? I've read two of David J. Linden books and loved them, but anything accessible to non-neuro STEM people would be great. e: I'm reading Flavor by Bob Holmes right now, it's really good! Dave Grool fucked around with this message at 02:08 on Jun 17, 2019 |
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Jun 17, 2019 01:38
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Ten Becquerels posted:Really interesting thread so far, thanks for posting. I'm doing my undergrad honours right now, looking at whether ageing has an effect on neuroinflammation following a systemic reaction (basically we're injuring mice with a myotoxin then seeing if the inflammatory response leaks into the brain and whether old mice have a differing response to young ones.) We're mostly focusing on macrophages and microglia since the group's research focus is primarily immunoageing rather than anything to do with neuroscience, but I'd be interested to know more about the kinds of effects ageing has on the brain and whether you think the immune system has effects on how the brain functions day-to-day? Aging and neuroimmune interactions is a really interesting field. A lot of this interest, at least to me, is because it ties in with the renaissance we're seeing with glia in the field. The basic process of aging in the brain is one of decline and degeneration, so in older brains you see lower neuron densities, lower rates of neurogenesis, that sort of thing. You also see a tendency for the microglia, the brain's resident immune cells, to become more reactive and pro-inflammatory. In fact we're starting to see the glia, microglia in particular, as playing a critical role in both normal aging and neurodegenerative disorder. For example, most of the main alzheimers risk genes are not expressed by neurons, but rather by glia and immune cells. The ε4 allele of APOE4 is a huge risk factor for alzheimer's, and as it turns out, APOE4 is expressed by astrocytes and microglia, not neurons. Microglia actually tend to accumulate around amyloid plaques in the alzheimer's brain, and this is initially a protective feature (they are able to phagocytose and break down amyloid beta), but eventually becomes a problem of its own because chronic microglia activation leads to a pro-inflammatory state that ends up being more damaging in the long run. In terms of the day to day interactions between the brain and the immune system, this is also a very exciting area, though I guess the truly "day to day" aspects of the science are under-explored, since researchers prefer to examine pathologies. We know that depression, for example, has a substantial immune component. To see why this is, consider the concept of "sickness behaviour". You can give an animal an infection to observe sickness behaviour, but in practice it's much more common to administer LPS (lipopolysaccharide), which is a component of the bacterial cell wall that stimulates a robust immune reaction yet is not alive or actually infectious. Animals exhibiting sickness behaviour actually act very similarly to how humans act. They lose interest in things that are usually rewarding like food, sugar water, sex, etc., (i.e. anhedonia), they become more sedentary, and perform worse on behavioural measures of depression and cognition. Behaviourally speaking, this really looks a lot like depression. And this idea has lead researchers to ask whether the immune system plays a role in depression itself. It turns out that it does, at least for some people. Many individuals with major depression have elevated levels of circulating cytokines (IL-6, TNF-alpha, C-reactive protein, etc.,), and also show exaggerated cytokine production if they are stressed (the usual method for inducing stress in a lab setting is a public speaking challenge). Also, there are some medical conditions where patients need to be administered cytokines therapeutically, and these often produce depressive symptoms. Neurobiologically speaking cytokine exposure leads to changes in serotonin, norepinephrine, dopamine, and also on important peptides like brain-derived neurotrophic factor (BDNF). Without getting into the exact mechanisms of how each of these effects works, I think the broader point, namely that depression may represent the brain engaging a pattern of behaviours consistent with being sick, is quite interesting. A lot of those sickness behaviours actually make sense evolutionarily. Moving less, avoiding social contact, these are things that could turn out to be protective to you and your kin if you really are infected. The condition of major depression doesn't have a 1:1 correspondence with all of these features, but the overlap does have promise therapeutically. All this being said, there haven't been any therapeutic breakthroughs coming from this research. Anti-inflammatory drugs have been shown on occasion to improve the performance of traditional antidepressant drugs like SNRIs. Similarly, there's some evidence that omega-3 fatty acid supplementation, which is also anti-inflammatory, might help antidepressants work. However, the drugs that directly target cytokine signalling are pretty heavy duty and really only useful for serious cancer and autoimmune conditions. So we haven't really found a way to address this directly, and as with all antidepressant schemes you should approach the field with a great deal of skepticism given how often these trials fail to replicate or show very small effect sizes. Hmm well I kinda got off on a tangent there, but I hope my answer is interesting and makes you think of possible things to study if you continue on in neuroscience.
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Jun 17, 2019 18:05
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johnners 2.0 posted:You mention appetite and hunger as one of your areas of study. As a Canadian experiencing legalized weed, and the munchies that is experienced, do you think there will ever be enough advancements that one could produce GMO weed to interact with our brains to eliminate this problem? There are two known receptors for cannabinoids. These are called CB1 and CB2. You find CB2 mostly outside of the brain, in immune cells and peripheral organs. CB1, on the other hand, is found all over the place in the brain, including in parts of the brain that control appetite, body weight, and energy expenditure. Because of this, CB1 is believed to be responsible for the munchies. CB1 is known to bind with THC, which is the primary psychoactive ingredient. But of course there are lots of other cannabinoids and interesting chemicals in cannabis, and anecdotally at least you do hear about certain strains that don't cause the munchies as much as others. So I think that you could produce a strain of cannabis that emphasizes these other compounds that might reduce or counter-act the munchies. We don't know much about those compounds, so I can't say how they'd work, but once such a strain was created, chemists would be able to identify the chemicals involved and neuroscientists could study how they work in the brain. I do think there'd be an inevitable tradeoff with psychoactivity though, since we know that THC is responsible for both the psychoactive effects and the munchies. So it seems hard to get rid of one side of that equation without also removing the other. oystertoadfish posted:i want to thank you for the detail in your responses as well. i learned something about MASCO! circadian rhythms are so rad The following is an attempt to answer both Johnners and oystertoadfish. I'm not sure if there's any single thing I've done that I'd really call unethical, but I do feel like being part of science in a trainee position forces me to participate in practices that I don't really like and might be ethically questionable. The main one of these has to do with animal husbandry. We breed huge numbers of mice every year because my lab uses several genetic models. Knockout mice, which are genetically engineered to have a particular gene removed, are complicated to breed. In my case, the kind of mice I use need to have two copies of the correct versions of three separate genes, but their parents can never have more than one copy of each, since being homozygous for these genes impairs breeding. This means that in the best case scenario, only abut 12.5% of mice born will have the right genotype. To make matters worse, we often don't use females, and they make up about half of every litter. So you're down to 6.25% of mice born are useful experimental subjects, and for a typical mouse litter size of 8, the odds are 50/50 that even a single male mouse will be born with the correct genotype. This means that we have to breed huge numbers of mice just to get enough subjects to use in an experiment. Mice with the 'wrong' genotype must be culled, or in certain cases can be used as breeders if they happen to have the correct genes for that. This process is incredibly wasteful, especially when a lot of research is based on flawed experimental designs that make it impossible to derive meaningful conclusions from the data. I actually don't like how mice are housed at all. Our mice follow the relevant federal and state guidelines, but those are pretty bare-bones. Mice live in groups of 2-4 in shoebox sized cages with some bedding, nesting material, and free access to water and chow. It's boring to the point where I suspect it is bad for the mouse's brain, and I don't think we really get realistic behaviours out of the mice. I would love to see more mandatory environmental enrichment like running wheels, tubes, and conditions that simulate foraging. In my field of obesity, for example, mice are usually made obese by forcing them to eat a mega high fat diet with no food choice, no opportunity for exercise, no chance to explore or forage for food like a wild mouse would. Unsurprisingly, under these conditions mice always get really fat. But we've been at it for decades and still haven't really solved obesity or any other such problems, and part of the reason may be that we're treating the mice like walking cell cultures rather than the complex animals they are. I can't even use rats anymore because they're so much smarter and friendlier than mice I can't bear to kill them or force them to live an unfulfilling life (I also used to have pet rats and so I've got a real soft spot). My goal for my own lab is to impose a higher standard of enrichment, including running wheels in every cage as a bare minimum. I also want to focus only on studies in wild-type mice using naturalistic manipulations instead of surgery or genetic modification. We'll see how that works out. Oh and speaking of cat torture, I've always thought that dogs would be a very valuable subject for studying social behaviour and disorders thereof. We've had dogs that seemed as though they were on the autism spectrum. Millennia of selectively breeding the friendliest dogs that have the most human-like behavioural features might mean that we could find some convergent evolution toward human-like structure/function in the social regions of their brains. Also dog breeds clearly have different 'personalities', and so studying how these breed-specific phenotypes manifest in the brain could be an interesting model of human personality and personality genetics. Of course actually studying dogs is unthinkable, I could never go anywhere near that and I'm sure most people would feel the same. We might look at doing fMRI and other kinds of imaging in dogs to make some progress though. funny song about politics fucked around with this message at 19:29 on Jun 17, 2019 |
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Jun 17, 2019 19:25
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Dave Grool posted:Any recommendations for pop neuroscience/brain stuff books? I've read two of David J. Linden books and loved them, but anything accessible to non-neuro STEM people would be great. Oh yeah I've got lots of book recommendations. One of my all time favourites that still really shaped my understanding of mental health is Why Zebras don't get Ulcers by Robert Sapolsky. In fact, anything by Sapolsky is going to be good (I'd also suggest checking out his lectures on youtube, or anywhere he's been interviewed in long form). Some others: In the Realm of the Hungry Ghosts - Gabor Maté ; A book about addiction written by a doctor working in Vancouver's downtown east side. The Noonday Demon - Andrew Solomon; An 'atlas' of depression including individual histories and some neuroscience In Search of Memory - Eric R. Kandel; A memoir by a Nobel prize winning neuroscientist who made major advances in the neuroscience of memory. Includes lots of details on the neuroscience of memory. Your Brain is a Time Machine - Dean Buonomano; Describes the neuroscience of how our brains keep time, perceive the passage of time, and also how time might work in the universe. I just read this recently and found it very fascinating. Anything by Oliver Sacks, but especially The Man who Mistook his Wife for a Hat, An Anthropologist on Mars, and Awakenings. There's definitely a lot more, but these are some of the books I've read that are so memorable to me that I could name them without consulting any of my lists.
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Jun 17, 2019 23:27
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Oliver Sacks should be tsken with a great deal of salt, because he extrapolates wildly from small pieces of information in order to make a good story.
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Jun 18, 2019 01:04
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Tunicate posted:Oliver Sacks should be tsken with a great deal of salt, because he extrapolates wildly from small pieces of information in order to make a good story. That's true, and I would extend that caution to pretty much every book in the popular science realm. I do like Sacks though, and I've always put him at the top of my suggestions list because I think he gives a very good window into how weird the brain really is. He writes case studies of unique syndromes and tries to infer deeper truths about how the brain works from them. They're not really scientific experiments with quantifiable measures or replications, they're just idiosyncratic syndromes that demand some kind of interpretation. I think half the value is just seeing how he thinks about the syndromes, what parts he finds salient, and how he uses it to understand the brain. The other half is seeing how the brain reacts to damage, and seeing how different aspects of our thought/behaviour/personality can be dissociated, changed, or even removed. That says a lot about how the brain works and how we ought to think of it. I've recommended his books to people with loved ones going through brain troubles and I've heard that they really help them understand something about neurology and why things are so difficult.
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Jun 18, 2019 03:39
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So I have ADHD and would love to know more about how that affects the brain from a neuroscience standpoint. In particular, I'd love to know how seemingly disparate symptoms like executive dysfunction, rejection sensitive dysphoria, and the more popularly known symptoms of inattentiveness and lack of focus are all expressions of the same disorder. This is a really fascinating thread btw and I'm disappointed that it lasted less than a page before the questions seemed to have dried up
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Jun 21, 2019 23:50
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ninjewtsu posted:So I have ADHD and would love to know more about how that affects the brain from a neuroscience standpoint. In particular, I'd love to know how seemingly disparate symptoms like executive dysfunction, rejection sensitive dysphoria, and the more popularly known symptoms of inattentiveness and lack of focus are all expressions of the same disorder. This is an interesting question because it highlights the disparity between the typical treatment strategies and the true nature of the condition being treated. This is pretty much par for the course in psychiatry, but in the case of ADHD the puzzle is that the dopamine system is directly addressed by the stimulants usually used as treatments, but the actual neuroscience of ADHD goes quite a ways beyond that. Drugs given for ADHD are usually things like methylphenidate (ritalin) or adderall (literally a mixture of amphetamine salts/isomers), which work primarily by causing the brain to release increased amounts of dopamine. Since the drugs seem effective, it leads us to believe that there are problems with dopamine signalling in ADHD. The dopamine system believed to be involved in ADHD originates in the midbrain and projects widely to higher levels of the brain (i.e. the cerebral cortex and important sub-cortical structures like the striatum). It's an interesting system, because there aren't really a huge number of dopamine-producing neurons, but because they spread dopamine so widely, they have a very large influence on brain activity. We normally think of dopamine as a 'reward' signal in our brain, but that's actually a pretty old fashioned way of looking at it. A better way of thinking of dopamine is that the brain uses it to indicate stimuli that are salient, unexpected, or worth learning about for some other reason, in essence "tagging" them so that the rest of the brain can react appropriately. There is an element of reward in this formulation, after all 'rewards' are best when they're unexpected, and the brain needs to have some kind of widespread signal to tell all of the parts involved in producing behaviours that whatever they just did was good and worth repeating. This understanding of dopamine casts a bit more light on the symptoms of ADHD. Impulsivity and temporal discounting of rewards (i.e. being unable to delay gratification for a better reward in the future), for example, can be thought of in terms of learning. They're situations where the brain is not doing a good job of assigning the right value to present and future rewards, and this is one of the things dopamine helps us do. This also feeds into executive dysfunction, which involves difficulty in stringing together complex sequences of behaviour or thought. It's possible that what we identify as executive dysfunction is really a combination of response disinhibition and delay aversion, in other words not being able to perform the correct behaviour at the correct time, and this ability is exactly the kind of thing that dopamine helps regulate. Neuroimaging shows that a surprisingly large number of areas throughout the brain are different in individuals with ADHD, and many of these areas are not direct recipients of dopamine, but may be directly downstream of areas that do use dopamine. In my estimation, ADHD is very much a "whole brain" condition. I'm not in this field myself, but it looks to me like the current thinking of the emotional symptoms of ADHD are generally brought under the umbrella of "emotion regulation", and treated as another manifestation of impulsivity and the general inability of the brain to exert top-down control over its emotional and cognitive processes. The anterior cingulate cortex, for example, which normally communicates with the amygdala to modulate emotional state, shows lower levels of activity in individuals with ADHD. This basic pattern thus mirrors the pattern we see for cognition. The executive regions of the brain (namely the prefrontal cortex) has a number of competing responses or tendencies coming up from lower regions in the hierarchy. With the help of dopamine, it is able to suppress certain responses, favour others, and generally tune the whole brain towards a certain goal or behavioural response. Emotion, though not really a 'behaviour' in the same sense, may work in a similar way, where the executive brain regions need to be able to wrest control from competing factions of lower regions and organize a coherent, appropriate emotional state. The same challenges that apply to executive control and attention could thus apply to emotions, and in fact there is a good deal of neuroanatomical overlap there. I should mention that if we correctly see ADHD as a whole brain condition, we can't limit our scope just to dopamine and the drugs that affect it. But since that's still what we have for therapy, and since dopamine regulates so many brain functions, it serves as a structuring theory. Hope this gives you some things to think about. I'm not an expert in ADHD so I tried to give a more 'narrative' review of the present understanding rather than naming all of the different brain regions and chemicals thought to be involved. Oh and I don't mind if the thread is a little slow, I always learn a lot from trying to answer questions, and even the amount I've had so far has made this well worth it for me, but thanks for reading.
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Jun 24, 2019 01:13
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Thanks for answering! So my interpretation of your answer would be, essentially, that ADHD is at its core the brain's dopamine regulation malfunctioning, and because that is such a major part of the brain, both in its day-to-day functionality and in the long term learning of behaviors and how the brain develops itself in general, this creates a massive system of knock-on effects that expands past dopamine regulation alone adequately encompassing the cause of the disorder. Would you say this interpretation is correct? The way I'm seeing it and theorizing based on your information, an ADHD infant brain is basically equivalent to an infant neurotypical brain, with the singular exception of dopamine regulation, but as the infant grows and learns that dopamine regulation difference causes the brain as a whole to develop differently. This theory would fit in line with my personal experiences with being diagnosed with ADHD, where as early as pre-K my teacher was telling my parents that I likely had ADHD, but my pediatrician said that it would be better to wait a few more years before attempting diagnosis, as at that young an age it's much more difficult to discern the difference between ADHD behavior and normal behavior. My next question would be, since your background is in the application of neuroscience to obesity, what's the brain science behind eating? What's the difference in brain activity between eating a juicy hamburger, eating a far too rich cake, eating a salad, and eating dirt?
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Jun 24, 2019 23:35
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ninjewtsu posted:Thanks for answering! So my interpretation of your answer would be, essentially, that ADHD is at its core the brain's dopamine regulation malfunctioning, and because that is such a major part of the brain, both in its day-to-day functionality and in the long term learning of behaviors and how the brain develops itself in general, this creates a massive system of knock-on effects that expands past dopamine regulation alone adequately encompassing the cause of the disorder. Would you say this interpretation is correct? The way I'm seeing it and theorizing based on your information, an ADHD infant brain is basically equivalent to an infant neurotypical brain, with the singular exception of dopamine regulation, but as the infant grows and learns that dopamine regulation difference causes the brain as a whole to develop differently. This theory would fit in line with my personal experiences with being diagnosed with ADHD, where as early as pre-K my teacher was telling my parents that I likely had ADHD, but my pediatrician said that it would be better to wait a few more years before attempting diagnosis, as at that young an age it's much more difficult to discern the difference between ADHD behavior and normal behavior. I think your understanding of ADHD matches with my impression of it, and I think with the broader understanding in neuroscience. We really don't know what an infant's brain looks like if they have ADHD and there has been a lot of effort to try to identify early-life predictors of future ADHD diagnosis. Things like infant frustration levels and emotional regulation, activity levels, and motor control have all been studied but as far as I can tell the link between these things and future ADHD diagnosis is pretty fuzzy. A role for dopamine in driving the normal development of the higher brain regions could explain the functional and neuroanatomical differences seen in ADHD brains, but it's difficult to dissociate this effect from environmental factors and genetics in humans. ADHD is very heritable and has a very strong genetic component. At any rate, this looks like a really promising area, but the implication is that if we think ADHD is something to be 'cured', we need to look at ways of achieving early diagnosis and some kind of intervention before the usual symptoms manifest, and currently no such method exists. Plus it would be ethically very unpalatable and potentially impossible, since I assume such a therapy would involve giving ADHD meds to babies who are not yet symptomatic. The neuroscience of eating is quite interesting. Since I'm a mouse neuroscientist, I'll probably focus mostly on that kind of research here. The basic behaviour of eating seems to arise from a combination of homeostatic and hedonic influences. The homeostatic control of food intake is primarily driven by the hypothalamus, and it relies on input from hormones, circulating nutrients, the time of day, stretch receptors in the gut, and so on to decide when an animal should eat, and roughly how much. The hedonic system, as the name implies, is concerned more with the reward value of food. This is the system that drives us to choose palatable foods like burgers and cakes over the more nutritious but less delicious choices. The best guess we have for why such a motivation exists is that we are hard-wired by evolution to favour nutrient-dense, calorie rich foods, and fat and sugar exemplify those properties. Pure sugar in particular is very rarely available in large quantities in nature, and it seems like our genetic calibration for how much sugar to eat is based on the idea that there isn't going to be much of it around. Obviously this is not the case in the modern world. The reward system I'm talking about here, by the way, is pretty much the same dopamine system that I was talking about with respect to ADHD. In addition to interacting with cognition and executive function, it also interacts with the more basic drives we have like food, drink, and sex. If you think about the 'negative' symptoms of ADHD, for example impulsivity, you can see that they are a kind of flip side of tendencies that our ancestors absolutely required for survival. Being impulsive is actually a very useful ability in the wild, because it allows you to temporarily suspend fear, reluctance, and better judgement to reach for something from which you may very well benefit. All wild animals need to take risks in order to feed themselves. When a mouse is full and not in need of anything, he's happy to stay hidden and safe from predators. But when food is needed, the mouse has to override its normal sense of caution and go out into the world to seek food, and this naturally has risks. We know that dopamine is involved in this calculation between effort, risk, and reward, and we know that more valuable food items (fatty/sweet/salty) are given a higher status in the brain's calculations. You can see, by the way, how having an effort/reward calculation that's mis-calibrated could lead to something like ADHD. My biggest question for the field isn't why people become obese. In fact it seems inevitable that we'd tend to get heavier and heavier as the modern world presents us with an insurmountable surplus of food that's scientifically designed to tickle our brain's ancient pleasure centres. The real question is why some people don't become obese. In my case, I've been skinny my entire life, even during long periods of time when I ate utter junk food. Nowadays I eat healthy and keep an eye on my calories, but it takes essentially no effort and no additional willpower to maintain my weight. I've noticed that if I go on vacation and drink all the time and eat junk food, at most I'll gain a couple of pounds, and those disappear automatically as soon as I'm back on my normal schedule. For people who struggle with weight, their story is similar except their body is always bringing them back to a much heavier set point. We know a lot about the mechanisms that regulate moment to moment hunger, but for all the hormones we know to be involved, none of them have resulted in a useful therapy. You'd think it would be simple. Take a hormone that we know goes up when you're full and makes lab rats stop eating and inject it into people trying to lose weight. Should work like a charm, but in every case these treatments have little to no effect, and the person inevitably becomes resistant to them after a while. Even after decades of study, we don't have any good reliable medical path to long-term weight loss apart from bariatric surgery, and even then people gradually start to regain weight. There's some kind of 'set point' in the brain that is able to pull on all of the levers of energy balance, i.e. appetite, cravings, energy expenditure, fat storage, physical activity levels, thermoregulation, etc., to force your body to hold a certain weight. Go on a diet? No worries, your brain will just lower your energy expenditure and subtly reduce your physical activity to save calories, all while burdening you with hunger, cravings, incessant thoughts of food. Start exercising? No problem, exercise doesn't even burn that many calories and your brain will scrimp and save energy during your off time, plus make you eat more, to make up the difference. Have part of your stomach removed surgically? Your brain will again scrimp and save on energy expenditure, and it could eventually get you back up near your original starting point even if it does it a few grams at a time. In my estimation, we know very little of where this set point is located, how its 'setting' is first established (though genetics and early-life nutrition play a major role), and how it could ever be re-programmed. This is the major challenge in the field, and I really don't think we're anywhere near an answer at this point.
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Jun 25, 2019 05:07
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that's really fascinating! i have a friend with POTS (Postural Orthostatic Tachycardia Syndrome), which hearing it from her, is a condition caused at its root by the brain miscommunicating with the heart, and making the heart behave in ways that don't match up with whatever physical state the body is actually in (google seems to disagree with her but i certainly don't want to argue with a friend suffering from a debilitating medical condition about the condition they have, based on info i got from 5 seconds of googling) i don't exactly expect you to be able to explain POTS since from my understanding it's an incredibly poorly understood condition, but i would like to learn more about how the brain regulates the heart and in what ways it does so and how it knows when to regulate it a certain way
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Jun 25, 2019 06:26
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What's the science behind ptsd?
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Jun 25, 2019 11:59
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ninjewtsu posted:that's really fascinating! I had a look at a clinical review article on POTS and it was pretty interesting. It's certainly not well studied in terms of mechanisms, and at least in the paper I saw there wasn't much talk about the brain being involved. Most of the proposed causes are in the peripheral nervous system, and these include things like autoimmunity, neuropathy, and genetic mutations affecting peripheral nervous system genes. Though at some level, it must also involve the brain because POTS has high rates of comorbidity with things like anxiety, somatic hypervigilance (i.e. being overly aware of everything your body is doing), chronic fatigue, and that kind of thing. The heart rate is regulated through the autonomic nervous system, a branch of the peripheral nervous system. This is basically a set of nerves that is anatomically separate from the nerves you have voluntary control over. The autonomic system connects to all of your internal organs, as well as to the glands and smooth muscles all over your body, and it operates with little to no conscious control. The autonomic nervous system (ANS) mediates basic physiological functions like heart rate, blood pressure, digestion, and also things like sweating, goosebumps, and countless other things. The ANS has two divisions called the sympathetic and parasympathetic nervous systems. These two systems have different anatomies (not relevant here though), and in a simplified sense perform opposing functions in autonomic regulation. The sympathetic system, when activated, tends to increase heart rate and blood pressure, whereas the parasympathetic system does the opposite. The heart beats by itself. In fact, isolated heart cells (cardiomyocytes) in a petri dish will show autonomous contractile activity. The contractile activity of all these cells is organized by an electrical system in the heart. So you don't even technically need a brain to have a heart beat, all the brain does is control the heart rate and various other factors. It can do this through direct connections between the autonomic nervous system and the heart, and it can also do this indirectly through hormones like adrenaline. Adrenaline is released by the adrenal glands (located on top of the kidneys) under the influence of the sympathetic nervous system. Blood pressure is modulated using a similar scheme, with the help of some other hormones that I won't go into. The brain senses blood volume using small organs called baroreceptors located primarily in the aorta and carotid arteries (i.e. closer to the head and neck). These communicate blood pressure to the brain. When you stand, gravity forces blood downwards causing these receptors to detect a sudden drop in pressure. The brain needs to take immediate steps to correct this imbalance, lest it find itself deprived of blood. So the brain orders the sympathetic nervous system to constrict peripheral blood vessels in the lower body, to drive blood upwards and raise blood pressure, and to increase the heart rate. This is a normal reaction, and it's absolutely necessary in order for us to be able to sit and stand normally without fainting. As far as we can tell, it seems like there's something going wrong with this reflex in POTS, but nobody seems to know why.
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Jun 27, 2019 05:15
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underage at the vape shop posted:What's the science behind ptsd? There's a lot to go over in this question so I'm going to try a bit more of a point-form response instead of a narrative. - Most PTSD research takes place in the context of men who have been exposed to some kind of physical or intensely violent trauma, usually in a military, first responder, or something like that. Another subset is in the context of survivors of violent attack, rape, victims of war, refugees, and that sort of thing. Military studies are favoured because they're easy to get funding for, and also the military is an ideal setting for a controlled experiment since so much data is recorded and the subjects are less variable. - PTSD has a genetic component. Identical twins who experience the same amount of combat have about a 28-41% rate of PTSD concordance. - Personality also plays a role. Pre-existing tendencies towards anxiety, as well as socioeconomic factors like lower education level increase the risk of developing PTSD following a trauma. - There's evidence that the hippocampus and ventromedial prefrontal cortex are smaller in individuals with PTSD. The hippocampus involved with forming memories, and both areas are involved in fear extinction. Fear extinction is a laboratory model designed to test how well animals can lose their fearful reaction to a given stimulus. If the fear system is working properly, subjects should correctly develop a fearful response to dangerous or scary stimuli, but also be able to lose that response if the stimuli eventually proves harmless. - Interestingly, the reduced hippocampus size may actually exist before exposure to trauma or the onset of PTSD. One study looked at identical twins, with one twin having had combat experience and also PTSD, and the other having no PTSD or combat experience. Surprisingly, both twins had smaller than average hippocampi! So maybe there are aspects of the brain's anatomy that predict risk of PTSD. - We know from studies of memory that the simple act of remembering an event makes that memory 'editable'. It's kinda like the brain loads memories from the hard drive into RAM, and while the memory is in RAM, it deletes the hard drive copy. This leads a lot of researchers to think that they could 'edit' PTSD-associated memories, or at least reduce their emotional valence. Guiding patients through a recall of their traumatic experience while administering beta-blocker drugs can potentially allow those memories to be re-encoded with less of an emotional response. I don't think this approach is having any kind of amazing effects when it's been tested, but it's possible that psychedelic drugs might do something if we ever look at them seriously. - Another spin on this is the fact that strong emotions put a sort of 'stamp' on memories, ensuring that they're much harder to forget, and cause much stronger responses when recalled. There has been some work looking at how to handle victims of trauma in the immediate aftermath (if you can get to them) to reduce this 'stamping in' effect. Again, the use of beta blockers have been tried as a sort of PTSD 'vaccine' to mixed results. There's also evidence that imposing a cognitive load, say by playing a challenging video game, could distract the brain enough to interfere with memory formation. There's also potential for stronger drugs like anticonvulsants or antipsychotics, that could temporarily disrupt memory formation in the immediate aftermath. - Blocking the formation of PTSD, which I should stress is not currently possible, has ethical ramifications. Who gets to decide whether an individual should undergo such treatment? Since you can't really predict the likelihood of PTSD in such a short time frame, are you sanctioning the eventual development of a Men in Black style memory eraser? Would we want such a thing? It's easy to say that trauma has value for personal growth, but PTSD is a very serious condition and I personally would rather have my memory dulled. Hope these points are interesting to you!
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Jun 27, 2019 05:40
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what's going on in the brain when you hear a funny joke? how does the brain determine if a joke is funny or not? what's the neuroscience behind comedy
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Jun 27, 2019 14:28
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While I don't have PTSD, I have a related thought/question. At 14, I witnessed something potentially traumatic. For the next ~11 years after that, I didn't seem to have any emotional issues related to it. But from ~25 on, related imagery has a chance giving me an emotional reaction. Is there something special neurologically that could have either shielded me for 11 years, or harmed me from that point on?
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Jun 28, 2019 02:41
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That was really interesting, and I'm a little sad that I really don't have the education to have a proper conversation about it with you. Thank you! I asked because I got it from stuff in childhood and was interested in what was happening in my own head. I think the part about difficult mental problems is really interesting. I did extremely well in school, because I threw myself at the work. The cause of my ptsd never really got better, but the stuff that causes the most issues is definitely from when I was younger, when I had no troubles with the school work. When school was hard, even though things were as bad as ever, the memories are less difficult if that makes sense. I also have congenital anosmia (olfactory nerve aplasia). I know smell is incredibly important for memory, could that have potentially played a role? I know that smelling things can trigger people with PTSD, I wonder if the anosmia was a blessing, in that I could spend relatively more time with those memories in therapy and less time being triggered because I'm straight up missing a trigger. Thus making it easier to change my association with those memories. Thats just me coming up with stuff several years after the fact. Personally, I wouldn't change anything that happened and in a way I'm glad it happened because it's definitely made me a stronger and more empathetic person. I'm also trans, having experience with dealing with mental health has made everything about being trans so much easier to recognise and deal with. Yeah it sucked, but it made me 'me' and I wouldn't change that. I'd be okay with treatment to block ptsd after an event in adults, but I'm not convinced that giving it to kids who can't make a fully informed decision is a good idea. I know I'd be a weaker, worse and probably much unhealthier person without going through what I did. I can very easily understand why someone would disagree. underage at the vape shop fucked around with this message at 12:03 on Jun 28, 2019 |
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Jun 28, 2019 12:00
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ninjewtsu posted:what's going on in the brain when you hear a funny joke? how does the brain determine if a joke is funny or not? what's the neuroscience behind comedy To be honest I don't think there's really been anything that convincingly explains the concept of humour or comedy from neuroscience. The basic underlying principle of comedy is the subversion of expectation. Think how the earliest form of humour a baby can recognize is something like peekaboo, and the expectation it subverts is basically object permanence - the knowledge that objects in the universe continue to exist even when they're outside of view. Vast portions of the brain are devoted specifically to predicting things in the environment and and organizing appropriate behavioural responses. So on a simple level it seems like a sense of humour for humans is almost a byproduct of the enormous energy and cognitive real estate devoted to predicting and trying to make sense of the world. If those predictions are subverted in a particular way, for some unknown reason we react with laughter and mirth. If you look at brain scans of people watching stand up comedy, you see activation of reward-related regions, some of the very same targeted by the dopamine system. This makes sense not only in light of the fact that the dopamine system is involved in pleasure, but also the fact that the dopamine system is heavily involved in predicting future rewards and guiding behaviour in the appropriate direction. The basic reflex of laughter, on the other hand, can be stimulated without accompanying mirth with some forms of direct brainstem stimulation. I think you will actually see unconscious varieties of laughter in the case of some brain injured patients for this reason. I don't think you can explain the broad psychology and neuroscience of humour without appreciating that it's deeply inter-woven with the basic cognitive traits that make us human. It's really quite an interesting thing to think about.
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Jun 29, 2019 04:29
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dirby posted:While I don't have PTSD, I have a related thought/question. At 14, I witnessed something potentially traumatic. For the next ~11 years after that, I didn't seem to have any emotional issues related to it. But from ~25 on, related imagery has a chance giving me an emotional reaction. This type of experience seems to be reasonably common, at least according to my reading of the literature. Researchers often will study people who experienced trauma from a major event, say a flood, school shooting, or some other kind of disaster. This allows them to follow up in lots of people with similar histories of exposure but with different rates of disorder. Anyhow, in people exposed to these sorts of trauma as youth, there's definitely a tendency for emotional and psychological symptoms to have a delayed onset, sometimes more than 10 years later. The psychological concept of repressed memories does not have any currency among modern neuroscientists or psychologists, so it's probably not that. The thinking, instead, is that early-life trauma sensitizes the brain and stress-associated hormonal systems. This primes the individual, making them more vulnerable to some kind of subsequent trauma or triggering event. Such an event may never come along, but in people with the right combination of vulnerability and later life exposure, even full-fledged PTSD can appear long after the trauma itself. I don't think we're too certain as to how this works exactly. There are genetic variants that contribute to the likelihood of childhood abuse leading to adult PTSD (to be clear, this phenomenon tends to be studied in extreme cases, we don't know if your situation is qualitatively different, or if it is analogous). There are also reports of either enhanced or blunted (different, at any rate) dexamethasone suppression test results* in survivors of childhood trauma. There needs to be more work done on understanding how early trauma can prime the nervous system for future problems. I have no idea why children or youth can sometimes experience a trauma and show no serious acute symptoms, but I think we need to recognize that a lack of outward expression does not rule out some kind of hidden inner trouble. * The dexamethasone suppression test measures your body's ability to regulate its levels of the stress hormone cortisol. Dexamethasone is like an artificial version of cortisol. Since it's chemically different, you can measure the levels of it and your body's own natural cortisol separately in the blood and compute a ratio of the two. Normally when you administer dex to a person, their body quickly shuts down production of its own endogenous cortisol so as to keep the levels of this stress hormone steady. If your stress response is disturbed, your body may not response to the dexamethasone and continue churning out cortisol on top of it, or it may shut down cortisol even in response to a very small dose of dexamethasone.
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Jun 29, 2019 04:55
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underage at the vape shop posted:That was really interesting, and I'm a little sad that I really don't have the education to have a proper conversation about it with you. Thank you! I asked because I got it from stuff in childhood and was interested in what was happening in my own head. This is really interesting. There's definitely a lot of work showing that individuals with PTSD have heightened sensitivity to certain classes of odours. In the case of combat veterans they're things like burning fuel or gunpowder, blood, and so forth. For people with other traumas, I imagine the odours are different but the basic principle holds. I looked around for a case study of a situation like yours but couldn't find anything. The closest I can find are some studies in rodents showing that the olfactory bulb --- basically the first brain structure to make contact with the olfactory epithelium and begin the process of processing odours --- shows structural changes in response to olfactory fear conditioning. In other words, if you pair a specific smell with a scary stimulus in a rodent, their olfactory system will change. Also, if you lesion the olfactory bulb somehow, olfactory fear conditioning is disrupted. That's not a huge surprise. Olfactory bulbectomy used to be a common old school method for inducing depression-like symptoms in rodents. Mice and rats rely heavily on their sense of smell to get around in the world, so you have to take all this research with a grain of salt when comparing it to humans. Nevertheless, since the olfactory system is so intimately tied in with the emotional and memory systems, this connection does make sense. Anyhow, rats with olfactory bulb lesions show reduced fear conditioning, suggesting that the formation of fearful memories involves the olfactory system in some way. We really can't extrapolate this to humans, but I really think your case is an interesting one and it would be really cool to find more people like you and see if there's a connection. There are a lot of tricky ethical questions to grapple with as we understand and control more and more of the brain. We're shaped by the positive and negative experiences in our lives, and I guess the ideal outcome is to reach a point of accepting that and loving yourself, while respecting the role your life's events played in shaping you. Still, I'm sure lots of people have thought, at various times in their lives, that they'd happily swallow a pill to make their brains more normal. I don't think such a pill will ever exist, but the line between "disorder that should be cured" and "natural variation in the human condition" is something that has changed historically, and it also varies between individuals.
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Jun 29, 2019 05:54
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funny song about politics posted:This type of experience seems to be reasonably common, at least according to my reading of the literature. Researchers often will study people who experienced trauma from a major event, say a flood, school shooting, or some other kind of disaster. This allows them to follow up in lots of people with similar histories of exposure but with different rates of disorder. Anyhow, in people exposed to these sorts of trauma as youth, there's definitely a tendency for emotional and psychological symptoms to have a delayed onset, sometimes more than 10 years later. I would also expect that it would be really difficult to secure research funding for this. Also I'm imagining trying to tell a joke to a mouse and its hilarious On a more serious note, if you don't need the money are you required to TA courses in order to get a PhD? I thought it was pretty interesting that my girlfriend only needed to teach two lessons when in the US all the grad students I knew were basically teaching half of a course. Xun fucked around with this message at 03:09 on Jun 30, 2019 |
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Jun 30, 2019 02:48
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Why do antidepressants kill the sex drive?
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Jun 30, 2019 05:53
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Xun posted:I would also expect that it would be really difficult to secure research funding for this. This is true for a lot of interesting questions unfortunately. Interestingly, rats (and presumably mice) do exhibit a form of 'laughter' in their ultrasonic vocalizations. Rats that have been gentled by routine handling are very friendly, almost like little dogs. You can tickle these rats and they'll make laughter-like sounds in response. I don't think it's a model for comedy/humour, but it was a somewhat unexpected discovery from when people began looking at ultrasonic vocalizations more closely. I think TA requirements are different for each school. I'm in the US now but I've noticed a lot of differences between how grad school worked in Canada vs. here. I think when I was in grad school you were not required to be a TA, but the department was required to offer you a position. Nobody ever turned it down, because the income is essential and also because it's good experience for future academic jobs. TAships had a set number of hours, but the number you actually worked depended a lot on your prof and what class they were teaching. I've had TA jobs with huge weekly workloads, and I've done others where all I had to do was proctor exams. As an instructor, I was a bit of a control freak so I handled most of the work my TAs would normally have done. That's not really a good way to do it, but as an early-career academic you live and die on your teaching evaluations, and I didn't want to risk having a bad TA drive down the experience for my students.
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Jul 1, 2019 16:56
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Davinci posted:Why do antidepressants kill the sex drive? I don't think the mechanism of this is very well understood. It's true that serotonin, norepinephrine, and dopamine, three neurotransmitters affected to varying degrees by the different antidepressants, play a role in sexual arousal and orgasm. It's also true that different kinds of drugs have different effects on sex. It seems like buproprion (Wellbutrin, etc.,) has the lowest rate of reported sexual side effects, and brain scanning studies show that compared to paroxetine (Paxil, etc.,) patients on buproprion have higher activity in motivational, emotional and autonomic controlling brain regions in response to erotic imagery. So the SSRI class of drugs seems to be worse than the other types like SNRIs. But beyond that I can't find much that addresses the "why" of this. I guess it's difficult to study in animal models, since the mouse's 'sex drive' is quite different from that of human beings. Another thing I've noticed is that this issue is studied more in males than females, even though it certainly affects both sexes. Up until recently, most drug testing was done exclusively in male mice, and so female-specific side effects and mechanisms have bee totally under-appreciated. It's also suspected now that these side effects in general are more prevalent than we think, because they tend to be under-reported unless patients are asked directly. Sorry I can't give more of a definitive answer. Like I said, the field seems a little but puzzled by this. We know which specific drugs and drug categories have the highest rates of sexual side effects, so we can make inferences based on their chemistry and mechanisms of action. And we know that sexual side effects are treated symptomatically with things like viagra for men, and lube for women. Those facts on their own show our ignorance as to the mechanisms, because if we knew why the problem happened, we could treat that instead of the symptoms (though this same criticism applies to the relationship between depression and antidepressants more broadly).
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Jul 1, 2019 17:29
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Interesting thread! I took Ritalin/ Methylphenidate for about three years and later experienced light spasms when falling asleep and also "exploding head syndrome". I heard this is related to the brain shutting down parts unsuccessfully. So did the amphetamines have had a negative effect on my brain? \/ e: Thanks for your input! lllllllllllllllllll fucked around with this message at 18:40 on Jul 3, 2019 |
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Jul 1, 2019 21:30
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What is depression's effect on the brain? What's the difference neurologically between a depressed brain and a normal brain? Is it just a deficit of certain chemicals like serotonin, or is there more going on like how adhd is more than just a dopamine malfunction?
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Jul 2, 2019 03:07
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lllllllllllllllllll posted:Interesting thread! Hmm this is very interesting! There's not really much literature on exploding head syndrome (EHS). It seems like it's more common than you'd expect, but under-reported. Some estimates of prevalence go as high as 10%. I wasn't able to find any reports of it developing as a side effect or consequence of methylphenidate treatment, but you do see EHS during the withdrawal stages from some SSRIs and benzodiazepine drugs, but the symptoms go away after the brain's chemistry has re-adjusted itself. It's also quite likely that your symptoms began coincidentally. There really aren't many theories of what causes EHS. One of the early theories, I think by the guy who coined the name, was that it was caused by brief disinhibition of the cochlea, or the regions of the brain it connects with. This could cause the sensation of a loud, sudden noise. This idea, by the way, relates to an interesting point about how sensory information is processed in the brain. We think of the sensory organs as "input" to the brain only, but most organs have reciprocal connections with the brain that help to tune their sensitivity. This may not be directly to the organ itself --- the eye doesn't have these --- but they might be to the first or second brain region reached immediately after the sense organ. These reciprocal connections help the brain exert 'top down' control on the earliest stages of sensory processing. But I don't think this cochlea disinhibition theory is believed by many people. The ability of some drugs to stimulate or treat EHS does give some hint as to its neurochemical basis. Withdrawal from benzodiazepines and SSRIs, respectively GABA- and serotonin-associated drugs implicates these neurotransmitters. Serotonin in particular is produced in a region of the brainstem that's also involved in regulating the sleep-wake cycle, so problems with this area could potentially lead to parasomnias and other sleep disorders. There's also evidence that EHS is exacerbated by stress, but we don't have any idea about the neurobiology of that relationship. I don't think methylphenidate caused any permanent effects on your brain. A relationship between this drug and EHS has not been reported as far as I know, and most cases of EHS are idiopathic, so I don't think there's anything to worry about. I'm sorry I can't be more helpful here, but the literature on this condition is very sparse. I guess it's because it's difficult to set up a study where you can directly observe someone's brain while they're having an episode.
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Jul 3, 2019 04:21
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