Lecture Five and I could not make it

Because I did not feel like it.

But is it better to do stuff when you feel like it? Or when you don’t feel like it? Does that build character?

Or is it harmful for productivity? I don’t know. I also really don’t care.

Frustration. Hate. But towards whom or what? Maybe people.

I don’t like people

Will go bicycling now.

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Lecture Four and Why I Like this Course

Just to begin: a serotonin based view on clinical depression is not enough. It sure is simple, beautiful, treatable, but just simply not true.

But before continuing on that, let me just say a thank you. This is truly an interesting course, because it makes me think. Because finally I have a possibility to think on my own and also to bring those thoughts out. Something that the university really doesn’t encourage – weird, because isn’t that exactly what we’re supposed to do here?

But yes. The lecturers balance each other out: it’s good to have a very rational (and sometimes even mechanical, sorry) to tell us how the mechanisms work. But then also to have a humanist psychologist who tells us how these actually manifest in our being. Now this is something truly remarkable, unifying the qualitative experience with the measurable mechanism. A great combination to reach true understanding. Exactly how neuroscientific research should also work.

But yes, back to the depression!

That whole thing leads back to the 60’s, the golden era of chemicals (and not just for hippies). That is when they found out about neurotransmitters and saw the correlations with different moods. Such as the one where serotonin levels seemed to correlate with happiness.

And there is surely some truth to this. We can just look at the raver’s who took serotonin-releasing ecstasy or MDMA in the 90’s. Yup, happiness in there. Just look at the smileys.

Then why SSRI’s don’t work? Elevated serotonin levels, but no response? I liked the idea of “the people needing time to think themselves” and I think this surely true. The psychological component should not and even cannot be removed in this kind of research. But when looking at the mechanisms behind that, I think it gets way more complicated than just increased serotonin levels.

First of all: emotions are a complex phenomena. Second of all: depression is way more than just “a bad mood”. Depression isn’t just sadness or melancholia, it is a persistent feeling of sadness and loss of interest in everything and all the time.

Well, in here lies the first clue – it is “persistent”. If it is persistent, then there is something constantly doing something in your brain, right?

Well, you could say that “it is the low serotonin levels”. Well, no. SSRI’s don’t seem to work very well for minor depression. Well, maybe it’s just not potent enough. But we have drugs that can very selectively release serotonin to your brain, such as MDMA, MDA or MDAI. What they seem to do, is not just increase your mood, but create a very interesting condition in you, referred to as empathogenic or  entactogenic by psychotherapeutists.

What we see, is the suppression of anxiety, disinhibition, empathy towards others, affection and sociality enhancement among other things. A perfect state to work on difficult personal matters, I would say. What a shame, that all these tools have been made impossible to be used because of the current legislation.

So, if this only comes from mostly serotonin, it seems to do a lot more in the brain then thought and should be as a lot more complex transmitter then “the mood transmitter”. Of course the above mentioned state is something we all would want to experience all the time, right? Free of worries and full of love? But it is not possible. Constantly elevated serotonin levels can cause life-threatening symptoms and the positive effects seem to diminish very rapidly after usage. In fact, major depression is a very common side-effect of continuous MDMA-usage.

But if not serotoning levels, then what is persistent in the brain? Well, you said it yourself already. It is the negative thoughts. The constant negative self-referential process that is going in your brain.

And what are brains constantly doing? They like to do this process called default mode network. Constant self-referention.

And this is where we should put our research and our treatments. To the breakage of the negative self-feeding loop and then the recreation of it into a new and healthier sense of self.

How do we do it? Well, therapy of course. That is the only persistent way. But we could use drugs too. But better than SSRIs.

The clinical effect of SSRIs is not due to increased serotonin levels increasing mood, but due to the enhanced plasticity it creates in the plain via glutamate connected process.

The big three of the amines – dopamine, noradrenaline and serotonin – should not be thought as “classical neurotransmitters” but as “neuromodulators”. In addition to many basic physiological fuctions, serotonin participates to higher brain functions, such as cognition and emotional states, by modulating synaptic plasticity via glutamate.

And plasticity equals the brains ability to create new connections. And new connections equal new thoughts. And new thoughts equal braking the viscous cycle of negativity.

Of course, mediating glutamate directly is a bad idea. It is toxic as hell. But there are better options.

I think this is why ketamine and other glutamate antidepressants show us promising results. It is due to antagonist effect on the NMDA receptors glutamate will release onto AMPA and other metabotropic receptors. This is effect is much more direct than the SSRI-directed and will thus be a lot faster.

In very treatment resistent depression, such as with terminal cancer patients another possibility would be to use the classical psychedelics, such as LSD or psilocybin, which seem to work directly on the 5HT2A-receptor.

The 5HT2A-receptor is interesting, because depressed people seem to have them a lot more than average person. SSRI’s seem to downregulate them too.

But these psychedelics seem to work immediately, and downregulation of synapses does not happend that fast. What is more interesting, is that even one session can provide long-lasting positive effects.

They seem to produce a very interesting state, with very deep and spiritual feelings of connectedness, which science still doesn’t know much about. The therapeutic effect could be mediated through the direct “breakage” of the brain’s rest state networks. Or something else – there is a lot to learn!

But back to the SSRIs again. They are not good for you. The constant exposure to high serotonin levels will cause “desensitisation” of those receptors, i.e. they don’t respond to stimuli that well or as fast. I think this is the mechanism behind the “blunting of feelings” that can too often be seen in depressed patients taking SSRIs.

Surely, you might not feel that down all the time anymore. But sure as hell you won’t feel the highs anymore either. And if you don’t have those ups and downs, you’re missing on life and it’s wonderful plethora of experiences.

For example, when falling in love, your serotonin levels will go up and then crash down, to create that craving of your loved one. Now if your serotonin levels are constantly high, your brain can’t create this experience.

You can’t fall in love.

And I think falling in love would be the best cure for depression.

P.S. I can gladly give you an presentation what serotonin (and other neuromodulators as well) does in your brain, but I think that is a time for a whole new blog post or a lecture. 🙂

[EDIT] Just researched more on the 5HT1A-autoreceptors and their effect on brain serotonin levels.

So it seems that SSRI’s in the beginning actually activate also a lot of these receptors, which are inhibitory for the neuron itself. I.e. by releasing more serotonin, the activated 5HT1A-receptor acts as a ultra-short negative feedback loop thus making the neuron release less serotonin. So the brain’s serotonin levels actually drop after taking the SSRIs. Only continuous exposure to SSRI’s will downregulate these autoreceptors and thus making more serotonin available in the synapse.

Which could explain the therapeutic lag. Which would actually mean that more serotonin in the brain equals better mood.

Fuck. Hypothesis is wrong!

Back to the drawing board…

Or maybe the situations is more complex? Or maybe there could be different kinds of depression mechanisms in the brain…?

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Lecture Three and Why the Hell I Am Running Out of Time All the Time

Lecture three. No ideas really here to write. Or actually, too many of them.

The lecture was nice and I really think that the multiplexing idea on neural signal coding is something that could happen. I still don’t know how it really happens or how could we make an experiment out of it.

Marko said that motor neurons have all of three of those firing patterns. Now there is something interesting. Don’t most of the motor neurons lie in the cerebellum?

And didn’t they just find out that cerebellum does not only have connections to the body, but to the cerebrum too. Maybe the cerebellum doesn’t only fine tune the motor commands, but our thoughts as well! Maybe those motor neurons that link back to our brain could be the multiplexing system of our cortex, allowing the other neurons to communicate on time divided channels?

I don’t know, but I’ve been fascinated with this idea during this week.

But fuck. Here is the biggest problem of our university now. Of our whole society to be honest. There simply isn’t time to spend any time on any thoughts or ideas. You just have to rush forward. Make exercises. Attend lectures and meetings. Gather points. Why? Just why?

When I have an inspiring idea, when I have the motivation, shouldn’t I follow that instead and see where it leads us?

Doesn’t everything we know about humans through introspection and our neuroscientific findings say that we are not machines, that should follow some rigid orders and timetables. We should be allowed to play with idea. We should discuss with other human beings.

More spontaneous things, I say. Less rigid planning.

That said, thanks for the lecture this week. It was really good. Unfortunately I couldn’t attend the exercise session, because I was too busy. Even though I would have wanted.

Go figure.

It’s a weird place.

This society.

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Lecture Two and the Unbearable Sluggishness of Sleep Deprivation

fter a long and nice weekend on a cottage with good friends, you’re filled with love and happiness, but usually this comes at the cost of hours slept. And if there is one thing I hate, it is doing something tired. The last thing you want to do on a Sunday evening, is spend it on a homework exercise.

Motivation zero, everything is sluggish, brain doesn’t work. Horrible. But also interesting: why do I force myself on this? Why the hell do I do something that isn’t at all pleasurable for me? And in fact, it doesn’t even yield any noticeable benefit. The incentive is small. This is something I think humans are very different from animals: we do a lot of stuff we don’t care about at all. For absolutely no apparent reason. Why?

At the same time this week I was reminded once again, how similar we are to animals when I went to visit Heureka. Its fascinating exhibition “Body Worlds”, showed us how animal bodies work. It is incredible what different animals can do with their bodies. How wondrous the variability is, how ingenious the adaptation to different living conditions is. Though, we are without a doubt the most adaptable animal on this planet. And this largely due to our brain, and not because of our bodies.

But then I started to wonder: how much do we actually think with our bodies? There are some very interesting hints. The cerebellum, which was supposed to only coordinate the fine motor movements, is actually largely reliable for higher cognitive functions too. Gut bacteria seems to have direct effect on your personality and mental health. And most of the serotonin receptors are located in the gut – not in the brain.

And this is why Tuesdays exercise sessions was so brilliant. Building the brain with play dough! Now this is what I call learning! Doing something with both your brain, and your body. The dream team. Literally, because they are both saying it is now way past bed time.

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Lecture One and the Hard Problem of Consciousness

This question always comes up on every single neuroscience course I’ve ever attended. It is a matter of debate with my friends every time it comes up. And a big fascination of all those lovely hippie friends of mine.

“What is consciousness?”, you ask and then the the Zen Master slaps you in the face and suddenly you’re enlightened. The question is extremely stupid because it already contains the answer.

Everybody feels what consciousness is, but no-one can quite define what it is. As the lecture quite well pointed out, we have to split this problem into smaller parts: consciousness as self-awareness,  as a social phenomena, as attention. As the philosopher: in order to study reality, we have to split reality into smaller parts and study them. But then again, that is no more THE Reality, is it?

But surely natural sciences are capable of understanding this probelm, you say! It is only our puny human mind that is able to grasp it. With the rational thought and gift of observation we will be able to pinpoint consciousness and reproduce it! As the physics have pointed out the laws of the universe, so shall neurosciences point out the laws of our own consciousness.

Well, no.

There are no physical laws. There never were, and there never will be. Or sure – there are. But only existing in your mind and nowhere else. Newton thought he was right. He had made the calculations and he had the models that could predict the movements of all beings in his Heavenly Clockwork.

Well then Einstein came up and destroyed that law. Time was not fixed, but relative? Gasp. Well, quantum mechanics are now destroying Einstein ideas.

But the universe doesn’t seem to care. It just goes on with it’s daily business. Because there are no laws. The laws you made up are models. Very good models, yes. Models that allows me to write on this computer. Models that allow us to fly even into space. But they are just that: models of prediction and nothing else. But to say that they are the laws of the universe is heresy.

But could The Reality be a formal system? Sure. I’m not saying that.

But aren’t our brains also made out of matter and part of this universe? Yes. Absolutely. What I’m trying to say, is that trying to define consciousness in terms of a model is impossible.

But we are so close! We have the answers and the models! Brain scans can prove it!

Well, lets say you did have the models. Let’s say we have an incredibly good model that can predict all of human behaviour and thoughts. Now who did that modelling? Who is the person thinking about that model? Can your model predict that the model is predicting itself predicting about it’s model? Now what you have, is a fascinating problem called a self-referential loop. If I am always lying, am I telling the truth? Go ask Kurt Gödel and see what he thinks.

But there is Consciousness. This is something you can be absolutely sure of. And we should talk about Consciousness to understand more about it. But what is consciousness then? Is is a separate part of you? Or is it that part who is doing the talking in your head? The one who does the continuous thinking and talking? Or the one that feels the happiness and sorrows of the world? Surely, if you think about it for awhile you will quickly notice it is none of these. They can be part of it, but they are not the whole.

But you are a clever neuroscience student. You will say that Consciousness is the collapser of the quantum wave function! Well, now we are getting somewhere.

But everything in this world is a collapser of the quantum wave function. In each and every object, each and every atom is collapsing the quantum wave of each and every atom. Thus even every single particle in each atom is a wave function collapser. But then why do we say that something isn’t conscious? I am conscious, and I’m pretty sure you are too if you’re reading this. But then where do you draw the line? Why animals wouldn’t be conscious? Why plants wouldn’t be conscious? Why everything wouldn’t be conscious?

But this what I am saying is of course again only a model of thinking. But thinking models, or philosophies, are useful for interacting in the world and for personal development. And which thought is more viable and fruitful: the one where we are only selfish genes fighting for our survival? Or the one where we are all one, only mirroring our own personal Truths in this Reality?

And that is why I love neuroscience. I love it how it is a real natural science studying humanistic phenomena  – Ourselves. It tackles the problem of existence itself in a very practical manner. The Other is always different for the Self. Your qualia, your personal Truth, remains in a sense always inaccessible to me. But maybe trough shared experiences and understanding, through systematic research and brain scans I can get a better glimpse on how it feels to be you.

And in here the biggest question remains, how will we use neuroscience? What are those models we will come up with it? Newton’s and Einstein theories are so important, because they are useful models in a certain part of Reality. They were essential for the development of our species. They are now essential for our technology. In the same way, the answers brought by future of neuroscience, should not be judged only for their factor of truth but by their usefulness as well. When we look into ourselves, the line between objective and subjective gets blurry and we must remain alert and skeptical yet truthful and honest.

Will we turn our findings into yet another religion of science? Will we use it mindread and control people? To suppress them even more of their own inner beings? Or will we use it as a tool for self-exploration and -knowledge? As something that could evolve the Consciousness of Humanity as a whole?

I will now get out of this library. Sun is shining and the life is good. There will probably be kids eating ice cream. And I’m pretty sure they know what consciousness is better than I do.

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