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“The Intuitive Mind is a sacred gift, the Rational Mind a faithful servant. We have created a society that honors the servant and has forgotten the gift.” ~Albert Einstein
I’m sensing a conflict. While the conflict is in part an inner-struggle, I believe that it’s also ongoing in Western science & society (though it’s not always acknowledged to be as such). What on earth am I talking about? I’m talking about the relationship between the rational and the intuitive intelligences. I am intentionally referring to the intuitive as a type of “intelligence” along with the rational.
To some this seems an obvious thing to do, but to others – the two words are themselves at odds. In fact, the belief of the latter group – that intuition is devoid of intelligence (and by extension legitimacy) – is at the root of the inner / personal struggle.
After all, I’m a scientist. In order to be legitimate, I can’t be hokey-pokey (and isn’t that what intuition is?). Skepticism is an important part of my investigative toolkit – and while I’m okay with hypothesizing, and exploring alternative possibilities, all the imaginative and intuitive theories of the world are, in the end, nothing more than theory if they are unsupported by data. Show me your evidence! Or in the words of physicist Richard Feynman:
“It doesn’t matter how beautiful your theory is, it doesn’t matter how smart you are. If it doesn’t agree with experiment, it’s wrong.”
Period. I defend and believe in this sentiment with every fiber of my being. I also believe that there is absolutely no good reason to disparage the role of intuition and creativity in the sciences. In fact, I believe that the spirit of scientific investigation itself is fueled by such things as: excitement (for the question), love (of discovery), joy and pleasure (of finding things out), fun (of exploring the unknown). Notice a common thread? They are all emotions! And emotions are, by definition, excluded from the realm of the “rational”
“Observation provides the empirical data used to form our conclusions, and also arouses certain emotions for which there are no substitutes – enthusiasm, surprise, and pleasure, which are compelling forces behind constructive imagination. Emotion kindles the spark that ignites cerebral machinery, whose glow is required for the shaping of intuition and reasonable hypotheses” ~Santiago Ramon y Cajal
So it is clear that one cannot really ignore that emotions, intuition, and the subjectivity of our beings, play in this game of discovery we call science. Did I just place subjectivity and science in the same sentence? Aaaaaah! I think I just cringed while typing it. Even if we acknowledge that we are inevitably biased as individuals, don’t we believe in an ultimate objective, testable truth out there? And don’t we believe in the power of the scientific method? of peer-review? Yes (mostly), yes…and yes (also most of the time for that last one but that’s another post for another day).
I’d like to draw your attention to an interview, aired recently by one of my all-time favorite science correspondents, Natasha Mitchell, over at All in the Mind. The interview this week was with Iain McGilchrist, a psychiatrist and author of the book “The Master and its Emissary” Interestingly, the subtitle of the book is: The Divided Brain and the Making of the Western World. In it, he discusses how (at least in Western society) we are growing more and more heavily dependent on a rationalized, de-contextualized, and consequently de-humanized point of view.
The main title of the book, “The Master and his Emissary” is intended as a metaphor (inspired by a Nietzsche story). The “Master” is used to represent the right-brained, contextualized, intuitive, big-picture and experiential point of view while the “Emissary” is representative of the left-brained, rational and logical point of view. Of course, McGilchrist himself is quick to point out that both sides of the brain perform varied and important functions and that these are simplifications of their roles. The point, however, is even larger than our society’s potentially increasing brain lateralization. In his own words:
“But I think because it [left-brain/rationalism] is so eloquent on its own behalf, it’s neglected to allow us to perceive that there are other very important things that need to be combined with it and that’s really the message.”
What a shame! Yet, I think it’s true. There are several examples around us both within science itself, and in mainstream society where we see a higher value and respect placed on “logical and rational” and a belittling of the “intuitive” – often writing it off as “new-agey”. Of course we need to be critical of claims, of course logic needs to be applied – but as McGilchrist stated in his interview… there is little to no danger that (at least as scientists) we will give up on rationalism. Perhaps our concern then, to redress the balance, ought to be that we have lost sight of the other type of intelligence.
Thoughts? Feelings? Do share!
We all know this from personal experience: some people are good at handling stress and others…well, they’re simply not. Present any two individuals with the same stressful situation and chances are they will respond differently. Of course no one is immune to the adverse effects of stress, but it’s true that some individuals are, on the whole, particularly susceptible to the adverse effects of stress, while others are, on the whole, resilient. It’s no wonder then, that neuroscientists are asking: What molecular changes in the brain play a role in mediating stress susceptibility or resiliency?
During the last couple of days at SfN, I had the opportunity to speak with Michael Lehmann [Poster RR13], a postdoc in the at the National Institute of Mental Health (NIMH), who asked that very question. In particular, Michael wanted to know whether environmental enrichment could buffer the adverse effects of stress (thereby mediating stress resiliency) and if so, he wanted to know what brain regions were involved.
His studies were done in c57bl/6 mice and the environmental enrichment (EE) setup included: hoops and running wheels of multiple colors and textures as well as various types of nesting material. Animals in the control group were provided with standard bedding and nestlet material. Both groups had continual and unlimited access food and water. After 4-6 weeks in their respective homecages (EE & regular), half of the mice from either group were subjected to social defeat stress over a period of two weeks, while the other half were simply left alone for two weeks. In total, then, there were four groups:
|(1) Environmentally Enriched (EE)||(2) Control (C)|
|(1a) Social Defeat (SD) Stress||(2a) Social Defeat (SD) Stress|
|(1b) No Stress||(2b) No Stress|
Following the two weeks of stress exposure, animals were put through a behavioral battery of tests to measure anxiety levels, risk-taking behavior, social interaction and depressive- like behaviors. The results?
Environmental enrichment (EE) mediates stress resiliency
There were no behavioral differences in any of these tests between the non-stressed animals (Groups 1b and 2b). In other words, the environmental enrichment alone was not sufficient to reveal any differences between the animals. Differences were apparent, however, between the groups who were subjected to stress (Groups 1a and 2a). The animals who were in the non-enriched environments displayed higher levels of anxiety and depressive-like behaviors in tests than did the environmentally-enriched (EE) group. In a series of follow-up experiments, Michael then looked at what brain regions differed in activation between these two groups (using the functional neuroanatomical marker Delta FosB) and found that EE mice (resilient to the effects of stress) mediated their responses via brain regions known to be associated with emotion and fear regulation.
Infralimbic Cortex (IC) is necessary for EE mediated stress resiliency
To further investigate the role of the infralimbic cortex (IC) in particular, Michael ran one last series of experiments. He lesioned the IC using idotenic acid (a substance with selectively destroys neurons) both before and after EE to determine whether or not the IC was necessary for the EE-mediated stress resiliency.
(1) Lesion –> Environmental Enrichment (EE) –> Social Defeat (SD) –> Behavior Tests (2) Environmental Enrichment (EE) –> Lesion –> Social Defeat (SD) –> Behavior Tests
Animals who received the lesion prior to EE, demonstrated changes in behavioral tests. They showed decreased levels of Delta FosB expression in the nucleus accumbens (NA) and the . That is to say, when the IC was lesion prior to EE-induction, the beneficial effects of EE-mediated stress resiliency virtually disappeared. On the other hand, animals who received the lesion after EE-induction, demonstrated no changes in behavior and no decreases in delta FosB expression.
What does it all mean?
Well, for one thing it certainly reinforces the idea that environmental enrichment has positive outcomes for the brain. Furthermore, the last two portions of Michael’s experiments demonstrate something entirely novel: the acquisition of stress resiliency and the expression of stress resiliency operate via two different pathways. In Michael’s own words: “After environmental enrichment if you lesion [the IC] it’s okay, because the expression of the resiliency is now residing in other brain regions – possibly in the accumbens, possibly in the intercalate cell islands of the amygdala…”
So, the “where” is to be determined. I’m sure there will be follow-up experiments, and when there are – I’ll be sure to update. Anyways, this officially concludes my official “SfN reporting”. This blog, though, isn’t going anywhere – so please do keep the feedback (the good and the bad) coming!
P.S. Photo Credit in “The Setup” section comes from this paper.
One last break from our regularly scheduled science coverage to report on a unique dining experience in San Diego. Tomorrow I will be resuming my science coverage! Look out for an interview with Michael Lehman for his recent work on environmental enrichment and how it plays a role in mediating stress resiliency through the infralimbic cortex. Read his abstract here.
As we didn’t get back to the hotel until 3 am Monday evening, the girls and I decided we needed to sleep in Tuesday morning. So, sleep in we did. Late Tuesday morning, we decided that before meeting up with our friends, we would stop somewhere closeby for some food. We found a place close to the zoo that had pretty decent ratings: Hash House a go go. The menu promised a good variety of brunch options, so…off we went!
Luckily, there wasn’t much of a wait at the restaurant (we were told this was unusual for this hotspot, but likely due to the fact that we were dining off-peak times). We decided to order our own main egg dishes with an extra side of pancakes to share. When Kira asked our waiter how many pancakes come in a stack, he simply replied: “It’s actually a single pancake, but it’s big enough to share.”
Ladies and gentlemen: I present the Understatement of the Year Award to Hash House -
I just have one question: At what point does a pancake cease to be a pancake and at what point can you classify it…as an actual cake? Aren’t there diameter restrictions? Depth restrictions? These pictures don’t even capture the gargantuan nature of these portions. That pancake was at least an inch thick.
Needless to say, we couldn’t finish it all. We had to request 3 to-go boxes and when that wasn’t sufficient, we asked for another two. We spent the rest of the afternoon carrying eight pounds worth of food around Balboa Park - and yes, we did take turns.
The best part about the entire experience was that even though we were clearly freaking out, our waiter was clearly unphased. I’m guessing they get the reaction all the time – still, I was surprised he didn’t give us more of a warning! At least we had some good laughs. Thanks Hash House! Next time we’re in San Diego, I’ll bring along three friends and we’ll order: one pancake.
A break from our regularly scheduled science coverage to report on an SfN social event + a slightly-bitter commentary on Yellow Cab service of San Diego….
So. Monday night finally rolled around- the night of the Lady GABA throwdown at Stingaree in downtown San Diego. The place was pretty crowded (as was anticipated) and the DJ was pretty good! A clip of some of the sing-along to the music below: ( note:it was dark, so this is more for audio than video really)
The party was slated to officially end at 2 am, so around 1:30 am, my friends and I decided we’d try to beat the rush and catch a cab back to the hotel. After waiting around a few minutes and realizing there were no cabs in sight, we decided to call one up. So, I called Yellow Cab. The representative assured me that there should be one there “soon” as there are “plenty of cabs in downtown”. Well. This statement, dear reader, was kind of… a lie.
After 10 minutes, a Yellow Cab did pull up – but another group of drunk friends flagged it down. “Wait…is that our cab?” my friend, Kira asked me. We weren’t sure, so while the group of 5-6 drunk friends battled it out over who should get in the cab we tried asking the driver if he had been called up or not (he shook his head no) – and quite unnecessarily, one of the girls in the group put up her hand to my friend’s face and said in a most condescending tone: “Honey, we got this.” We should have just gotten in the cab while their friends were arguing it out. Hindsight is a powerful thing.
So after another 10 minutes, I called up Yellow Cab again. I spoke with the same lady who assured me that our cab was on its way – “Number 63,” she said to me, “it should be there soon.” Alright, well – at least we were altogether. We waited and waited, then waited some more. Finally, after forty-five minutes of waiting, I called up, yet again.
It’s unfortunate that I didn’t get the same lady because it was really she who deserved to get a piece of my mind. Instead, someone named Robert answered the phone. I began to explain what happened and he responded unperturbed and quite matter-of-factly: “there aren’t any cabs available.” When I told him that not only were we assured at the outset that there were plenty of cabs available, we were given the specific number of a cab (63) – he said, “she lied to you.”
Indeed. Well, dear reader, you may be wondering if I tried calling up another cab company at this point. I did. I called Orange cab. No lies this time. Just someone who told me that there was no one he could send out but that we should try walking to the Mariott next to the Convention Center to see if we could find any out there. So, we begrudgingly, began ambling our way over. If a picture is worth a thousand words, then a video is surely worth a hundred thousand.
There is a happy ending to the story. About a minute after I ended the recording, Staci and Kira were finally able to hail a cab (hallelujah!) and when the driver turned up the radio and “Promiscuous Girl” started playing, we didn’t even care. We were warm, we were off our feet, and we were finally heading back to the hotel where some warm beds awaited us.
[photo credit: John Hersey of NYTimes]
So I think we’ve established this much: in order to understand the biological-behavioral interface, we need to better understand epigenetic processes. More specifically, we need to know: Which epigenetic marks are transmitted transgenerationally? And how are they? Which marks are stable and which marks can be erased? What genes are susceptible to de novo methylation and what environmental factors (chemical, nutritional, hormonal, behavioral…) mediate these effects? Furthermore, how do these processes vary over space and time? [or in scientific jargon: what is the spatio-temporal specificity of these marks?]
These are just some of the questions scientists are facing as they attempt to break ground in the emerging field of epigenetics in neuroscience. Of course, this in no way implies the mechanism itself is new – to call it emerging simply means our awareness of this as a mechanism is emerging. So take any of the questions above, try to crack it open and what you’re likely to get (in addition to some hopefully useful data): even more questions.
Okay, so it’s complicated. What’s new, right? It seems obvious to state that the brain, genetic networks and the relationship between all these pieces is, well, complex – and yet, sometimes it’s the obvious truths that need to be stated. Truths that are obvious, tend over time, to be forgotten as we proceed along the investigative journey – especially when it comes to using (necessarily) reductionist methods to discover the functional components of a larger and complex, whole.
So this morning, at the minisymposium “Transgenerational Inheritance and Epigenetics: Animal Models of Neuropsychiatric Disease” that’s exactly what Dr. Tracey Bale, researcher at the University of Pennysylvania and chair of panel, did. She then launched into the data her lab has begun to unearth in an attempt to answer the following question:
What is the critical window within which induced maternal stress will affect male offspring at various gestational periods?
To answer this question, her group presented various stressful stimuli to the animals, then ran behavioral assays on the male offspring during early, middle, and late gestational periods. They found that the behavioral readouts (anxiety tests, spatial learning, etc) were sex-specific (hinting at an imprinting mechanism). They followed this observation with a scan to look at genes which showed sex-specific differentiation in expression. 96 genes revealed sex-specific expression, 32 of which appeared “demasculanized” (assessed based on angio-genital distance and testes-weight measures). This observation that the up or down regulation of certain genes was sex-specific, prompted the group to look at microRNAs.
Why? MicroRNAs (miRNA) regulate about 30% of protein-coding genes and they are enriched on the x-chromosome. Also, miRNAs are present in high levels in sperm (facilitating a mechanism whereby maternal stress effects can be transmitted through the germline and result in a measurable phenotype in the male offspring as adults). What did they find? 4 out of 329 miRNAs scanned for sex-specific responses to stress showed changes in expression levels. They went on to discover that these 4 miRNAs had one major common gene target (with various other targets as well) How’s that for specificity?
So what does it all mean? miRNAs can target gene expression in the brain of males in the F2 generation – in other words: this is proof that stress-mediated epigenetic changes can be transmitted across generations. I’ll let you chew on the public health implications of that one.
Today’s Special Presidential Lecture was such a treat! Every once in a while, we’re lucky enough to find something which engages us such that as we listen, we find ourselves almost literally sitting at the edge of our seat… hanging on to every word in an effort not to miss anything.
[image above taken from: "The Hidden Life of our Genes" movie]
Paolo Sassone-Corsi began his lecture entitled: “Joining the dots: Epigenetics, Plasticity and the Circadian Clock” by introducing Conrad Waddington’s term “Epigenetic Landscape” The idea is that cells with the same initial genomic profile develop into distinct cellular subtypes. The metaphor is that of marbles on a hill, where the marbles are the cells and the landscape of peaks and valleys represents an added layer of regulation (in this case: epigenetics).
It’s the “path” which the marble takes down the ridges and valleys of the landscape which determine the “fate” of the marble (i.e. where it will end up = what kind of cell it finally becomes). Won’t discuss this in this post: but one can see how the marbles going “back up the hill” then corresponds to the re-programming of stem-cells back to their “pluripotent” state.
After reviewing the structure of DNA, chromatin and epigenetic marks, and the ideas of Waddington, Sassone-Corsi began to paint the audience a picture of how what we traditionally understand and refer to as epigenetics, works in concert with circadian-regulated mechanisms in the body in order to increase or decrease plasticity.
“At least 10-15% of all cellular transcripts oscillate in a circadian manner,” he noted and “most of these are CCGs.” He went on to explain that this indicates a larger mechanism of regulation at play. In other words, epigenetics had to be involved. In their investigation of how circadian rhythms and epigenomic expression were coupled, they discovered that SIRT1, a nicotinamide adenin dinucleotide (NAD(+))-dependent HDAC, functioned in a circadian manner.
If SIRT1 sounds familiar – it’s because it’s found in red wine and is known to regulate aging, inflammation and metabolic processes. “It’s the French paradox,” he said “the French eat fatty foods and are still healthy because they drink red wine.” Don’t get your hopes up, though. He was quick to say, “this doesn’t mean you should drink too much!”
There’s a lot more detail and ground I’m not covering here – but I’m pretty sure I hit the main points. Here’s an excerpt from one of his abstracts: “Accumulating data show that chromatin remodeling events may be critical for providing specificity and plasticity in circadian regulation, and metabolic cues may be involved in directing such epigenetic events.”
I’m going to have to sit down and read his actual papers after the SfN meeting rush is over, to fully appreciate and grasp the implications of these findings. I encourage you to do the same! More blog posts on this topic are sure to be upcoming…