Neurology

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What? Were you thinking?

Ugh.  It’s a new day—and a Wednesday, at that, so I have to do the payroll.  It’s a new month, too, so there’s rent and water and electric bills and eventually cable bills and all that coming soon.

I suppose it’s nice that the vernal equinox is this month, and thus the beginning of Spring in the northern hemisphere.  And of course it’s nice that my brother’s birthday is also coming up this month (and one of my best friends from back home has her birthday before that, but we haven’t interacted in a long time).  But other than that, I have no interest in any of it.  Frankly, I don’t have much interest in anything at all.

I spent about ten minutes scrolling through my Audible app this morning, trying to find something I wanted to listen to on my way to the bus stop.  I didn’t find anything, though I have a fair few Audible books—not as many as I have Kindle books, but still, there are quite a few.

I eventually just returned to a podcast that I had started yesterday—an old one with Anil Seth on Sam Harris’s podcast, two interesting people talking about interesting things.  I get a bit frustrated when Sam betrays some of his bias toward the “hard problem of consciousness” being a legitimate, persistent thing, which I think is just a notion he holds onto as a meditator and thinker about consciousness—the notion that there’s something pseudo-mysterious about the fact that neural processes give rise to actual subjective experience.

I don’t understand what he thinks the alternative is.  The so-called philosophical zombie thought experiment is self-contradictory and incoherent when you look at it closely*.  How would a self-monitoring and flexible, self-directing, agentic, information-processing system that’s part of a biological organism with problems to solve and a not-completely-predictable world in which to live be expected to function?  It monitors itself internally and externally, including monitoring at least some of the contents of that processing, because that’s a useful thing for an organism to do to survive and reproduce in a complicated world that includes other beings like itself in addition to predators and prey and whatnot.  Why is it a hard problem that all this produces “subjective” experience?  What do you expect it to do?

It’s not any more sensible than asking why there is something rather than nothing.  What do you expect?  Obviously, there are only people asking that question if there is something.  And why would there be “nothing”, anyway?  Why do people assume that’s the default state?  Of course, I don’t think any actual, conscious being can truly imagine “nothing”, anymore than any conscious being can really imagine or contemplate the experience of ceasing to exist.

If you’ve been under general anesthesia—particularly really deep general anesthesia like you have for open heart surgery and the like—you’ve experienced the temporary cessation of pretty much all of your brain functions.  Try to remember what it was like when you were under complete general anesthesia**.  If there’s something for you to remember, then you were still conscious, and that means you weren’t under complete general anesthesia.

Alternatively, try to remember what it was like (for you) long before you were born, before even your parents were born***.  That’s what it was like not to be conscious.

From within its own realm, consciousness is, in a sense, endless, because it doesn’t feel itself begin and it doesn’t feel itself end—it’s almost like one of those Penrose/Escher diagrams of infinite hyperbolic spaces contained within another, finite space.  And this, of course, may very well describe the configuration of our own universe, since GR allows for spaces that look finite from the outside but are infinite from within, and mathematics can deal with them rigorously and consistently and thoroughly.  It’s not readily intuitive without a bit of thought and practice, but why would one expect it to be****?

Anyway, that’s the sort of irritated but at least engaging argument I get into within my skull with people who are not actually present with me, and with whom I’ll never interact.

When I try to talk to people at work about such things, I just get blank looks and confusion.  I tried to bring up my discussion from a week or so ago—regarding the M-theory related notion I had of a potential explanation for “dark matter”—with the smartest person I know in the office.  It was disappointing.  I was actually enthusiastic—I get that way about science and math, still, sometimes—but though he listened intently and politely, he said that it all really just went over his head.

It’s very frustrating, and quite disheartening.  I really do feel like a stranded alien castaway, sometimes, and in many ways, I always have.  This is part of why I always liked the villains in stories, not because they were bad guys—who cares about that?—but because they were always different, but strong and confident nevertheless.  They were people who got things done and changed the world, and who, by the way, also didn’t let other people fuck with them without cost.  They were strange, they were weird, but they were powerful and capable, though often not in productive ways.  And they’re fun, at least, or they used to be.

Nothing is very much fun, anymore, to quote the Pink Floyd song One of My Turns.

The next few songs on that album are Don’t Leave Me Now (too late for that) then Another Brick in the Wall, Part III, which definitely resonates with me, and finally Goodbye, Cruel World, to end the first half of The Wall, one of the greatest concept albums ever made.

The very fact that Pink Floyd’s only number one single was Another Brick in the Wall, Part II, the least good song on that album (though it’s got a great guitar solo…of course), is just another example of how unutterably stupid and worthless the world is.

Goodbye, cruel world, indeed.  And good riddance.

hyperbola hyperbole

*Just because one can utter the words of a “description” of what a philosophical zombie is and make it syntactically correct doesn’t mean the idea makes sense.  I can write 2+3=12, or say it, or whatever, but given what we mean by those symbols or words, it’s not a coherent mathematical statement.

**Not what it was like when you were just going under or gradually coming around.  Don’t be an idiot.

***Not any nonsense about past lives/reincarnation.  Don’t be an idiot.

****I think people tend to exaggerate, quite severely, just how complicated hyperbolic geometry really is.  (Get it?)

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I blog not you, you elements, with unkindness

Hello and good morning.  It’s Thursday, February 2nd, and the day of the week on which I’ve long done my semi-traditional blog posting.

I don’t know whether I have the energy to hunt for a Shakespeare quote to alter and/or a picture to put at the bottom, both vaguely related to whatever “subject” I address in the blog.  But, of course, by now, you readers will know what decision I, the writer, will have made, even as you read the words I’m writing while I do not know.

It’s a bit wibbly-wobbly, timey-wimey, isn’t it?

Of course, the biological experience of time is much more malleable and irregular than the actual nature of time, but time is not a simple, straight, linear dimension.  It’s warped by the planet beneath your feet, among many other things.  Your physical body’s tendency to want to follow the most “direct” path through it‒and the fact that the planet is in the way, preventing you from following that path‒creates what we call gravity, locally.

When you’re free-falling, you’re coasting through time (and space, of course), and it’s the ground that actually accelerates you once you reach it.  It’s a hell of an acceleration if you’ve been pursuing your geodesic unimpeded for long by the time the ground throws itself into your path.  Human’s aren’t built to withstand that kind of acceleration.

I’m writing with my smartphone again, today, by the way.  It’s just too annoying to deal with the laptop at the bus stop.  I also wrote more words than I really had meant to write yesterday, probably because I type faster on the laptop, but I don’t think the increased number of words was associated with an increase in actual content.  I think the signal-to-noise ratio, if you will, of my blog post yesterday was lower than it has tended to be with the phone.  That’s not an objective measure, however, and others may disagree.

As for my thumbs, they already feel a bit better than they did, and they’re not giving me too much trouble now.  I have some Voltaren cream (or is it an ointment?) that I can apply to the joints if necessary, though I already take round-the-clock NSAIDs every day for my chronic pain, so it’s not really recommended that I add the Voltaren, a strong NSAID in it’s own right.  It increases the risk for kidney damage and liver damage and stomach issues and so on.  But I’m already at risk for those things (though I take Omeprazole for my stomach protection) and I don’t see easy short-term solutions to the problem.

This is one of the conundrums (conundra?  Probably not) that make opiates and opioids both necessary and yet culturally difficult‒our non-psychoactive pain medications are literally toxic to our bodies above a quite low threshold relative to their analgesic powers.  Yet pain does not easily just go away on its own in many cases‒biology is subject to much stronger pressures for pain to persist than to allow it easily to be relieved, and those incentives will remain so in any evolutionarily stable form of life.

Opiates and the like can work against nearly any degree of pain with limited direct toxicity, but with diminishing success and tolerance, requiring increasing doses over time*.  But they do affect neural circuitry, reward, and motivation, among other things, and so their use is complicated‒and it’s additionally complicated by the fact that the treatment of pain, physical and psychological, is somewhat taboo in our society.

The use of various substances in one’s own body is even criminalized, and so black markets arise to take advantage of the inevitable demand.  And without matters being out in the open and subject to expert scrutiny and monitoring and education, various abuses and issues relating to lack of access to appropriate guidance and treatment and support arise and worsen.

And they will persist.

Do you think continuing to criminalize the use of drugs of various kinds will decrease abuse and death and even violence related to the drugs?  You hypocrites!  I say to you that it is the criminalization of that use that created the black markets and abuse and danger and sordidness‒and, indeed, the majority of the deaths‒in the first place!

You punish people for trying, however imperfectly, to treat chronic pain and those who suffer from it from addressing it, and are surprised that sufferers turn to the market you have created for illicit meds.  You have the temerity to be “shocked” that people die from the unmonitored, unregulated, inexpert use and manufacture of these things which you have removed from the bailiwick of expert awareness and oversight and monitoring.  You took an area that should have been medical and made it criminal and are stupid enough to be surprised that opportunistic criminals (whether they be gangs or governments or otherwise) are not as careful and caring as actual medical professionals.

And sometimes you are so hopelessly moronic as to imagine that further punishments of both producers and suppliers‒and even users‒of drugs will change the problem or decrease it or make it go away.  As if making an already suffering person’s life even more difficult and miserable is going to diminish their urge for relief and escape from at least some forms of pain, and their willingness to risk the permanent end to their pain that is death by overdose.  I’d need to exist macroscopically in all the ten spatial dimensions of M Theory to be able to give that the eye roll that nonsense deserves.

Phew.  That was a heckuva tangent.

I don’t actually use opioids or related medications, though I have been prescribed them in the past.  They interact with my rather peculiar nervous system in ways I find truly unpleasant, though they can help with pain.  So, instead, I suffer constant daily assaults on my kidneys and GI tract and my liver, and I accept that.

It’s not as though I will seek treatment if my organs fail.  I have no insurance, for one thing, but also, I just don’t see any point in trying to preserve my existence.  Heck, I’ve been told I have a possible recurrence or deterioration of my congenital heart problem‒I’m not fully convinced that it’s really any kind of recurrence‒for which I had heart surgery when I was 18, but I have no interest in pursuing possible further exploration or treatment of it, anyway.

Let my kidneys fail, let my liver fail, let my heart fail!  Blow, wind, and crack your cheeks!  Why would I try to preserve or prolong my existence when I don’t even like myself, let alone have anyone else nearby who likes me and spends time with me***?

Anyway, that went off the rails pretty quickly, didn’t it?  It also got longer than I expected.  Sorry.

I still don’t know the answer to my initial wondering about titles and pictures‒but you all do.  And I love you for it.

TTFN

windstormandmanscaled

*Though at least they don’t directly poison livers and kidneys, and the needed doses don’t keep going up without limit, though they are nevertheless often higher than most doctors are willing to prescribe.  This is largely because doctors fear having what happened to me happen to them, and who can blame them?  The only exception to this general hesitancy is with cancer.  People with cancer are allowed to be treated with whatever level of pain medicine it takes to reduce their pain, because in the typical human “mind” having cancer pain is different, and people with cancer are special.  They’re allowed to be dependent on pain medications, because surely they have the only type of pain that can go on and on without resolving and can steal all the joy from their lives, eventually killing them.  Anyone else is just a disgusting drug addict, a scum of the Earth, and deserves merely contempt**.

**The latter portion of the above paragraph is sarcastic.

***I cannot blame them, so don’t be defensive on my behalf.  I find myself infuriating and disgusting.

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If anhedonia becomes interesting, does it thereby destroy itself?

Okay, well‒sigh‒it’s Friday.  This week has already been about two years long, so I’m relieved that it’s coming to its end and that I have tomorrow off.  If something surprising were to happen and they asked me to work tomorrow, switching weekends with my coworker, I would hope, I would want, to say “no”.  Knowing me, of course, there’s a very good likelihood that I would go along with it, because I’m stupid that way*.

It’s not as though I have any sense of looking forward to the weekend, other than that I’m intellectually glad that I’ll be getting some rest.  I’ll probably take some Benadryl to help me sleep, which, yes, I know, does interfere with circadian rhythms and sleep cycles and all that jazz, but at least it lets my body rest for a short while.

I don’t really get any relief or joy from sleep, even when I get enough of it, though I understand that many people do.  Many people really look forward to sleep.  The only time I ever enjoyed sleep was during the time I was taking Paxil, which didn’t last long, because it had untoward side effects (and coming off it gave me my personal experiences with sleep paralysis that inspired a scene from Outlaw’s Mind).  While I was taking it, though, I got real joy, both anticipatory and actual, from going to bed and from sleeping, though I was in the first year or so of medical practice, so I did not sleep all that much.

Nowadays I don’t really get any joy‒anticipatory, actual, reflective, or whatever‒from much of anything, let alone from my quite limited periods of sleep.  I’ve been having more and more trouble even finding books that I have any pleasure reading.  Even non-fiction, now, has become difficult.  I have well over 400 volumes in my Kindle library, and I am dismayed to feel that there’s nothing there that I want to read.  And when I go to Amazon to look for new books on subjects that I have previously enjoyed, there’s just what seems like recommendations from the dusty, dingy, tiny little book aisle of an old K-Mart whose manager doesn’t read nor understand people who do.

I’ve long known that I’m not a very good match for the algorithms of places like Amazon or Netflix.  They never have done a good job at finding things to show me that I want to read or watch.  This is despite my having bought those hundreds of books on Amazon.  Netflix is worse, or else they just don’t have many things in their library in which I have any interest.

To be fair to Amazon, the last time I went into a beautiful, two-story Barnes and Noble, in which I spent over an hour looking around, I left without buying a single book (or anything else).

YouTube does a slightly better job.  It even introduced me to the nature (and possibility) of Asperger’s Syndrome via the inscrutable exhortations of its algorithm.  But either that algorithm has degenerated or I’ve chewed through most of the material in which I have any potential interest, but In any case, I’m getting diminishing returns from YouTube.  And now that the BBC has canceled Mock the Week, I don’t even have new clips from that to enjoy.  Even I can only go through comedy panel show clips a finite number of times before I lose interest.  And they keep offering me the same two compilation videos over and over, no matter how many others I know exist, because I have watched them all.

There are certainly inefficiencies and errors in their algorithms or deep learning systems or shallow learning systems or whatever the fuck** they’re using.  But a lot of it is probably a problem*** with me.  I’ve always had peculiar tastes relative to most of the people around me, and I think that’s gotten to be more the case as time has progressed, which is what time tends to do.

Mind you, if I’m with someone I like or love and doing something they enjoy, I can enjoy it with them, and indeed, I’ve always had a fairly broad ability to do so.  But those days are past, now, as I have no one I like or love around me, and I don’t really have a desire to find any new such people.  It’s just not worth the effort‒the return on such speculative investment is quite low, and the inevitable long term cost and injury is almost always severe.  I don’t have to walk across a hot stove too many times before I just stop walking on the stupid stoves.

So, I’m corralled into a seemingly increasing region of anhedonia****.  It would be a rather pleasing irony if someone could get real joy from sharing their thoughts and experiences about and with anhedonia.  That seems unlikely to happen to me, though.  Therefore, I’m going to call it done for today and for this week.

I hope you all have a nice weekend.

*That’s far from the only way I’m stupid.  Like all other finite beings (which is all beings as far as I know) I am infinitely stupid, in the sense that there is a functionally limitless amount of information and understanding that I do not have.

**Note to all autocorrection people:  I rarely discuss any member of the family Anatidae.  I am, however, inclined to using profanity to express things more grittily than by “ordinary” words.  There is neurological research pointing toward the idea that this is legitimately different in the effect it has on the one swearing and the one hearing (or reading) the swearing.  Why do you think people with Tourette’s syndrome sometimes have coprolalia?  There are, to my knowledge, very few tics where someone involuntarily shouts out, for instance, “She loves you, yeah, yeah, yeah”.  Unless that were to mean something profane in their society.  Someone with OCD might do so, but that’s a different kind of disorder.

***Reminder to self: look up the etymology of probably and problem.  In what specific ways are the words related?  Do they come from the same roots?

****Are there any fictional characters called Anne Hedonia or similar?  There really ought to be.

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“Hump Day” calls to mind a camel’s back, which we know can be broken by a straw

I’m starting this post at the house, seated on my “piano bench”, as I did a week or two ago when it was quite cold out.  It’s not cold today; it’s already over 70 degrees (F).  I just want to minimize the potential time in which I have to worry about the “shouty” lady, who really hasn’t been shouting so far this week, but has been laying around at my “usual” bus stop.

She was still there when I got back to the bus stop last night at about quarter after eight.  So she had been there for at least 15 hours yesterday, unless she wandered off during the day, which is certainly possible.

Anyway, that’s not very important, I just feel too socially awkward to want to have to worry about being approached by anyone, let alone someone to whom I can offer no consolation for what are surely myriad troubles.

I want to keep this post relatively short, because the last few have been absurdly long, especially considering the fact that I’ve been writing solely on my phone.  I think it can’t be encouraging for casual readers if I write thirteen to sixteen hundred words every day.  It would be one thing if there were significant substance to the posts, a deep analysis of some topic, but they’re just random, meandering blather.  That’s best in relatively small doses.

It’s only Wednesday, but the week already feels so very long.  I’m mentally exhausted, though physically I’m getting slightly more fit, walking 4 or so miles a day, sometimes more.  But even physically, yesterday I was in exceptional pain, even for me, all up and down my left side, focused on my lower back and hip but down to the ankle and up to the arm.

My whole left arm felt not just painful but numb, and was even vasoconstricted.  My left hand was pale and cool to the touch compared to my right hand, confirmed by a coworker.  I don’t know what I did to trigger it, but it was apparently some form of what they used to call causalgia, if memory serves.  I do have an old soft-tissue injury to my left shoulder that never completely healed.

I don’t think I can do this‒meaning, anything‒much longer.  I’m coming up on the last chance to get a “message from the universe” in the form of the most strikingly palindromic possible recording number yet, at the office.  I’ve missed all the others‒as expected.  Palindromic eight digit numbers are a rarity, especially when the first three to four digits vary only slowly.

Of course, I don’t really think the universe is capable of, let alone inclined to, deliberately send me a message in the form of a recording number.  This is really more like a game of chance I’m playing.  It’s not quite a variation on Russian Roulette, but it’s not really that far off, either.

I don’t want to let anyone at work know the nature of my game*, lest they try to fake an outcome for me.  I don’t think they would succeed, but they might try.  Of course, if I got even a hint that they were doing such a thing, I would just call the “game” off and consider it lost‒or won, depending on your point of view.

It’s sort of like how most people would say I won the game of Russian Roulette I played more than 10 years ago, but I sometimes think of it as having lost.  Very little net good has happened to me in the intervening years.  I won’t say there weren’t good things, but it’s been an unquestionably net negative, and the slope of that curve doesn’t look to be changing, certainly not in the positive direction.

Oh, by the way, those last two paragraphs were written at the bus stop.  The shouty lady is nowhere to be seen (or heard), and while I’m slightly concerned and hope she’s okay, I’m glad not to have to stand for twenty minutes while waiting.  My back and hips already hurt this morning, but it’s primarily on the right side today.  It’s good to keep some variety, to keep one guessing.  We wouldn’t want the pain to be boring, would we**?

Anyway, it’s also drizzling a bit this morning, so it’s good to be able to get under the bus shelter.  The water doesn’t bother me, but it’s hard to write when you have to keep clearing raindrops off the phone.

Okay, it’s become more than a drizzle, now, and the bus will be here in about five minutes.  I guess I’ll call that good for today.  It’s not good; very little has been good for me in a while.  But we’ll call it that.

Rest would be good.  Sleep would be good, if it were restorative, or at least entailed true oblivion.  I want to go to sleep.

*They already know my name, so there’s no need for them to guess it.

**That’s a slight joke.  Sometimes one hears of pain described as “boring”, meaning it feels as if something is drilling into or through some body part.  There are so many delightful and multifarious types of pain in this world, aren’t there?  It’s enough to make you want to throw up.

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Bus stop, waiting, she’s there, I say, “I think you’ve mistaken me for someone else.”

I considered writing this post this morning directly onto my WordPress site, which is something I almost never do.  But that would require a change of pace from my usual practice, so I’m not going to do it this time.  That’s largely because I have an already existing “change of pace” today, in the form of some person yet again lying down on the bus stop bench.

It’s very annoying.  I mean, I’m sure it’s probably annoying for that person, too, but I’m not the one that put them in that position‒I am all but mathematically certain of that‒but that person is the one who put me in the position of having to stand at the bus stop (and finally sit cross-legged against a tree, which put one of legs to sleep) with my back and hips and knee and ankle really giving me trouble already, writing my stupid ass blog post that maybe 5 people will actually read if I’m lucky.

By the way, there’s even someone at the “alternate” bus stop as well, apparently.  It never rains but it pours, as they say.  They talk too much.

I don’t know if anyone has actually read The Dark Fairy and the Desperado so far yet, but I’ve seen no feedback on it.  Maybe it’s so bad that no one can get through even the modest part that I’ve written so far.

I’m still struggling to find interesting things to read; most of the science books I have are dull to me now, though I reread The Coddling of the American Mind recently, almost all the way to the end, and it was good again.  I also got a new “biography” of Radiohead, titled Radiohead: Life in a Glasshouse after one of their songs, but it took me less than a day and a half of highly interrupted reading to finish‒maybe three hours, tops‒so it was engaging, but very brief.

I’m trying to start rereading Stephen King’s 11/22/63, which I remember being quite good when I read it once before.  So far it’s not bad, but I don’t know how long I’ll stick to it.

I have a modest amount of trouble with the premise.  Not the time travel thing, even in the atypical way King sets it up.  That’s fine.  It’s imaginative, and he recognizes and has the characters recognize‒and mainly just shrug in confusion, which is appropriate‒the apparent paradoxes.  It’s a horror story, not science fiction, so it’s not important to get into the nuts and bolts of this curious phenomenon.

No, I have trouble with the notion that changing any event in history could have any impact on any cosmic level of stability whatsoever.  I think the question of whether JFK hadn’t been assassinated only seems Earth-shattering to people who lived through it, and for the most part, the course of events doesn’t change much in any case.  I suspect most Gen Z “kids” barely know who JFK was, any more than they know who Andrew Johnson was, or Pepin the Short, or Phillip of Macedon.  Really, why should they know or care?

I mean, yes, history can be quite interesting, and it is good to know history, so we can try to see‒to the best of our ability‒the way events have flowed, and the sorts of mistakes and failures and successes are possible.  But this is all still parochial knowledge.

The universe wouldn’t care at all if the Cuban Missile Crisis had led to World War III or if a much more devastating all-out global thermonuclear war had happened at the peak of the arms race in the 80’s and wiped out civilization*.  Frankly if another asteroid the size of the K-T asteroid hit and drove 70% of all Earthly species extinct, including humans, it wouldn’t matter to the universe…indeed, if another huge impact such as the one hypothesized to have created the moon literally wiped out all life on Earth and reduced the surface to a new, partly molten “Hadean” phase again, the universe would not notice.

Probably.  Very probably.

I think this notion that human deeds could endanger some kind of cosmic balance is just hubris and delusion, harking back to pre-Copernican worldviews, though I’m quite sure King is not literally so deluded.  But this focus on humans (and human-like) things may be why King can never quite pull off the Lovecraftian, cosmic type horror, in which humans come to realize just how tiny they are and that even the “gods” of reality are not in any way anthropomorphic.

Though even in Lovecraft, having such “gods” is a bit of anthropomorphizing of the universe.  But then, a merely dead and bleak universe does not make for a very interesting story.

Still, maybe that’s one of the reasons Stephen King is so much more generally popular than Lovecraft‒because in his worlds, the deeds of humans are not only important to humans, but they can have cosmic significance.  And his bad guys are mostly very much human as well, in their character and motivations‒even the Crimson King and It.

His scariest stuff, to me, anyway, is his material along the lines of The Shining and Pet Sematary, where the evil forces are quite otherworldly, quite different, and though they certainly have malice toward humans‒the Overlook does, I’ll be bound‒even the “ghosts” in the hotel are not really the source or center of the evil.  They are, if anything, just the spiritual husks of souls that the hotel‒whatever it is‒had devoured in the past, like the empty carcasses of insects in a spider web, or perhaps like trophies on a hunter’s wall.

Well, that was a meandering and surprising turn through my head.  It’s curious sometimes to see what will trigger what.

By the way, I think that was the same woman from before who was sleeping at the bus stop, because she woke up just before the bus came, and she asked me something.  I thought she was seeking bus fare at first, and I had to tell her that I use a monthly pass, so I don’t have any cash, but then she said something about needing to stop the buses running because of something to do with a wedding.  I tried to tell her I didn’t understand, and she repeated part of it and then asked if I had heard from the children about the bus and the wedding.

All I could do was tell her I think she had mistaken me for someone else.  As I suspected before, I’m pretty sure she is mentally ill, with some manner of schizophreniform disorder.  Though I’m not a fan of interacting with strangers, she certainly didn’t make me feel frightened at all.  She just made me feel sad.

It’s very sad to think that not only is there nothing I could do for her in my present state, there would be little anyone could do for her even in the best of circumstances available in the modern world.  Mental illness is terribly difficult to treat, and it doesn’t get nearly as much scientific interest and resources as it should merit, as with so many other things.

It’s far more “important” to humans to have brand name shoes and mocha lattes and Frappuccinos from Starbucks** and to own the newest iPhone (same as the old iPhone), and to follow “celebrities” and to buy their ghost-written books.

That’s probably part of why even “cosmic” level horror stories, with rare exception, make humans so important.  Humans are delusionally self-important in reality, and want even their fictional horrors to be likewise.  And so, humans will continue to deceive themselves about their inherent importance, and vanishingly few of them will realize that, if humans want to become cosmically important, it’s going to be up to them to make it happen.

They aren’t inherently important, except to themselves (which is perfectly reasonable), and it seems vanishingly unlikely that any space faring, extraterrestrial civilization (if such a thing exists) will come to save humans and show them the way.  Why would they?  At most, they might send some disguised observers, anthropologists in the literal, outside sense.  Xenobiologists, from their own point of view.

All right, that’s enough for now.  It’s too much, actually.  I don’t have any idea what my point is.  Which may, ironically, be the point.  Or maybe I’m crazy, even beyond the illnesses of which I’m aware, and this is all just a hallucination.

What a dreary, disappointing hallucination that would turn out to be.  It’s not even scary.  Even the truly dangerous things in the universe are banal, dreary, and not all that impressive.  One would expect paranoid delusions to be frightening.  But I guess that would depend on how much the amygdala and related structures are involved in the disease process.

Enough.  ‘Tis done. 

*That’s the sort of thing I grew up being afraid of and feeling completely powerless to prevent.

**Why is there no apostrophe in the title of the coffee giant chain?  Is it meant to imply that there is more than one Starbuck, or indeed that each customer is a Starbuck?  It strikes me as lazy and slipshod.

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Where does a true blog wait? At the bus stop, sometimes.

It’s Friday again, and‒again‒I’m sitting at the bus stop, writing this blog first thing in the morning while waiting for the bus.

That woman who was screaming on a few previous mornings is screaming in a different region of the intersection now.  At this point, I honestly suspect she’s actually mentally ill.  There’s also a person with some form of fidgitiness or movement disorder or just some anxiety syndrome who has come and sat on the (small) bus stop bench not far from me.  I suppose he might either be on some kind of drug or withdrawing from some kind of drug, rather than having a primary disorder, but the woman is almost certainly mentally ill.

Of course, there’s not much one can do for her unless she asks for help or is openly a danger to herself or to others.  Actually, in Florida, even if she needs help, and asks for it, she’s probably out of luck.  Public services are rather limited here, despite this being the third most populous state in the US, and obviously quite wealthy.

The man I mentioned before couldn’t sit still for long before he got up and walked away, across the road to some other place.  I don’t know if he was hoping that I would speak to him or some such, and gave up when I didn’t even look at him other than in peripheral vision, while writing, or if he really was just stopping to rest.  If that latter, well, more power to him.

This end of the nation’s dong isn’t especially hospitable, so you should find rest when you can.  I would like to find some rest.  It would be so nice to go to sleep and to stay asleep through the night and wake up in the morning feeling refreshed rather than just groggy and resigned.

I do wish at least that this state were just a little less full of desperate and disgusting people.

I’m talking about the people in the state government when I say that, by the way, not people such as I mentioned above.  Also, some of the voters are a bit contemptible, the ones who imagine that they are solely responsible for all their own prosperity, even though the vast majority of them have not even a superficial grasp of how the universe into which they were extruded functions, from the subatomic to the cosmic, from the unliving vastness of intergalactic space down to computers and medicine and information technology and chemistry and biology and electricity and automobiles and the internet/the web and even television.  I don’t know how so many people can apparently stand not to know about these things, let alone sometimes still act smug and self-righteous.

As for troubled people like the shouty woman and the fidgety man, well they just make me feel a bit sad, really.  I mean, I don’t want either one to intrude upon me writing this blog post‒and neither one did, by the way.  Even when the shouty lady ended up walking past, in front of me, she was just muttering something about “catching the bus when it’s free” or something (as far as I know, it’s never free).

If I had unearthly powers, I would probably try to provide some help to either or both of them; I certainly gave a lot of money and stuff away when I was in medical practice.  That’s a big part of why I had to go with the public defender’s office (well, it’s an adjunct office, actually, but it’s the same idea) when I was charged with the bullshit I was charged with.  I was never very good at taking care of myself for my own sake, and I’ve gotten worse at it even since then.

So many people are so grasping and parasitic.  There are people in the office who regularly come to me for medical advice‒and even OTC treatment‒even though it’s thanks to the government of their poxy state that I can’t practice medicine anymore.  Cat forbid that they take responsibility for learning about and seeing to their own health.

From time to time, I think that I’m too high-functioning a person really to have any autism spectrum disorder‒but then, looking back at the things that happened to my life, and the way I have done things, especially once my separation and then divorce happened (and at many of the ways I managed things before then) when I was down here in Florida, far from my family and friends and everything, and when I realize how hard it is for me to arrange and keep track of the functions of daily life, I think…yeah, that ASD stuff actually explains a lot.  Knowing it doesn’t make it easier to counter, but I prefer to understand things as much as I can.

It’s not as though I don’t understand, intellectually, how things are done and how to do them.  I’m able to understand a lot of things.  But I can’t seem to pull myself or anything together, I can’t seem to organize my life or deal with ordinary things.  I can write novels and stories and blogs, I can write and perform and record and even produce songs (the latter not to a terribly high standard), I can draw, sometimes pretty well, and I can practice medicine and do science and operate computers…but I can’t promote my own works or stand to seek out anyone who would help me do so.  The social aspect of such things veers toward horrifying for me.

I’m able to survive‒often I don’t really want to survive, very often I don’t want to‒but thriving seems beyond me.  As Radiohead sings, “I’m not living, I’m just killing time.”. That’s from True Love Waits*, their last song from their most recent album, though the song itself has been around a lot longer.

Anyway, the bus will be here soon, and I will ride it, then ride the train, then walk, the trudge through the day and reverse the commute process at the end.  And tomorrow, since I have work tomorrow, I will do much the same.

And on Sunday I will do laundry, and then on Monday the cycle will begin again.  Sisyphus, eat your heart out!

Actually, that sounds more like a job for Prometheus than Sisyphus.  Are there any mythical figures who specifically eat their own hearts?  Whence did that expression arise?  I have to admit that I do not know.  It doesn’t really matter, but if anyone has any reliable information about the origin of that expression, I’d be glad to learn.

In the meantime, have a good day.

my bus stopadjusted

P.S.  The fidgety man just got on at a later bus stop from where I waited.  I think he just didn’t like sitting still, or perhaps he didn’t like sitting next to me.  It’s hard to hold it against him.

*It’s not a promise or anything optimistic.  The full title verse goes, “True love waits in haunted attics.  And true love lives on lollipops and crisps.”. In other words, the notion of true love is not something to be taken very seriously.  It eats like a child and “lives” like a ghost.

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Introspection, Extrospection, Emergence, Reductionism…let’s call the whole thing off.

I’m sorry about how long yesterday’s post was.  It’s amazing, as I think I’ve mentioned before, just how much I can write‒on my phone, no less‒when I literally have nothing planned about which to write.  Small wonder that, when I do have a subject, or a story to tell, I tend to write perhaps too much.  Though I guess that assessment is really the individual reader’s to make.  Some may think I’ve written too much, and some may think too little.  Most will never know because very few people know about my books at all, and I have no knack, nor money, for self-promotion.

Speaking of stories, some woman was standing in the street median across from the bus stop, screaming as if in heated conversation at 5:20 this morning (just now, in other words) about someone having cheated on her after having gotten her pregnant.  If this were twenty years ago, I would have thought she was psychotic.  Nowadays it seems safe to draw the tentative conclusion that she is actually talking to someone on her smartphone‒though perhaps that’s a misnomer for such devices when they are used for such purposes.  Honestly, why do people even want to be with other people?  Everyone is so pathetic, and I’m certainly no exception.

There are those who say that an appetite for delusion is necessary for people to find any will to live at all‒from delusions about their driving abilities and personal attractiveness to delusions about meaning in the universe.  And there are those who speculate that one of the hallmarks of clinical depression is a diminution of that ability to delude oneself, particularly about oneself.  Perhaps.  It’s probably not quite so simple as that, but that does capture at least part of the character of the experience.

Oh, well.  It is whatever it is at root.  The underlying causal structure may have little resemblance to the overarching phenomenon.  Nerve cells don’t resemble little brains, individual starlings don’t have the appearance of tiny murmurations, and water molecules do not in any way resemble ultra miniaturized oceans.

The materials to which the laws of quantum mechanics directly apply do not behave in ways that are analogous to any “large” phenomenon which they engender when gathered together and interacting in their trillions of trillions of trillions of trillions, etc.  Anyone who finds this surprising at all has really not thought about things very hard or very clearly.

It may be fallacious to imagine that a wave function collapses when measured, or when it interacts with other “particles” and decoheres; it may be that our experiments of such things are simply too artificial to capture the nuances of the immensely common submicroscopic interactions of such fundamental things (though I don’t doubt that they actually have bearing on how quantum mechanics behaves).

The problem with concepts like imagining that, for instance, the Copenhagen Interpretation is “correct”, and that measurement and observation is what causes the wave function to “collapse” is its implicit assumption that if we cannot “see” something in any strong sense, it can’t be considered “real”.  To me that seems an astonishing level of hubris and narcissism, especially from a species as pathetic and benighted as humans.

By this I do not, by the way‒and this is very important‒mean to open the door to subjectivism and any relativism of objective facts, or any version of the “perception is reality” bullshit.  There is all the evidence anyone might need that there is an external reality, utterly independent of any consciousness that might or might not perceive it.  But its nature is not necessarily directly perceivable all at once, or understood at first glance.  It requires rigorous detective work.

How did I get on that subject?  By stream of consciousness, I suppose…or perhaps it would be more accurate to say that it was by the stream of the unconscious, bubbling away and spilling over onto the surface of thought.

That stream is not like a stream of clear water, though.  Perhaps it might be said to resemble turbid water, but often it seems more like thick paint.  We can only see the surface of the stuff, but that doesn’t in any way imply that the interior doesn’t exist.  It’s merely not directly accessible to our eyes.

Then again‒and this applies also to what I was writing earlier‒the process of seeing and experiencing that sight is a neurologic process that is constrained by inputs from sense organs, not a direct, unmediated apprehension of the world outside.  Mere photons, unprocessed, can only deliver chaos to any random bits of photosensitive material they might encounter.

Thought‒of some form or other‒is required for sight to be in any way useful, or even actual, to any organism.  A closed-circuit TV camera and monitor do nothing but send signals, and cannot interpret or act upon the information.  If no one, or no program, or no other mechanism is being influenced by the information in any sensible way that affects its outcome, it might as well be a camera pointed at the surface of an uninhabited planet and sending those signals to a screen on some other uninhabited planet.

Again‒or still‒I don’t know what, if any, point I’m trying to make.  Probably nothing worth delving into too deeply, so I won’t bother with it much more, I think.  Instead, I’ll switch topics.

In the past, I’ve asked about whether people would want to have me write more of Outlaw’s Mind or The Dark Fairy and the Desperado.  One particularly astute reader pointed out that it was impossible to make any reasonable judgment without having the opportunity to read any of the latter story.  So, I think I’ll post that story here, all in one go, if I can fit it.

Don’t worry, I’ll insert one of those “continue reading” clickable thingies after the first few paragraphs.  Otherwise, it would be a ridiculously long blog post to get past if one wanted to scroll down to the previous one.

This doesn’t mean I promise to write more of it or of Outlaw’s Mind, or to write Changeling in a Shadow World, for that matter.  I haven’t yet figured out even how to check the results of my poll, and I’m pretty sure that it can’t be all that difficult, so don’t expect much.

Hell, I don’t even promise to keep writing this blog.  I’m getting tired of it, as I’m getting tired of pretty much everything, and particularly of myself.  There’s very little to be gained by pursuing anything at all.  But, perhaps, by posting DFandD, I’ll at least create the pseudo-closure of having all of my fiction to date be out there somewhere to read.  In case anyone wants to read it.

So, either I’ll post that later today, or I’ll just use it as my post for tomorrow.  I guess you’ll find out, if you care to look.

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Even the bus route isn’t a prime number

Well, it’s Monday morning, the second Monday of 2023.  I’m probably going to stop keeping count of such things pretty soon, so if you’re interested, you’ll need to keep track for yourself.

I hope you all had an excellent first weekend after New Year’s.  I myself did not.

I won’t get into the specifics, but remember how I said that I was considering changing my daily schedule so that I would take the bus to the train to work and then back again?  Well, that change has been forced upon me by various circumstances, mainly related to my own mental fatigue.  It turns out that I wasn’t feeling as rested on Saturday as I thought I was‒that was apparently an illusion brought about by the fact that I was so chronically fatigued that a slight increase in sleep duration‒brought about by having taken half a Benadryl, in this case‒gave me a foolish sense of false well-being.

So here I am at the bus stop now, waiting for the first bus of the day.  Unfortunately, it arrives about half an hour later than my memory of its schedule, but it’s been a long time since I took it, so I guess I shouldn’t feel too bad about that.  I’m waiting for the southbound bus.  I think it must have been the northbound bus I was thinking about when I thought it arrived half an hour earlier*.  In any case, I’m quite a bit early even for that, because I woke up and left the house at my usual time.  It looks like I won’t even be close to catching the first or even the second train this morning.

I had been thinking about buying a new bicycle, and if I took such a means to get to my usual train station, I might make the second train of the day, but then I would be lugging a bike around, and I would also get quite sweaty from riding.  That’s not the worst thing in the world, but it’s slightly annoying.  Still, it would be faster than the bus in the long run.

Of course, I could just plan to get up later in the morning, and come to the bus stop closer to the appropriate time, but sleeping late enough in the morning is not something at which I’m that skilled or gifted.

As for writing…well, at least I am probably going to finish this blog post in plenty of time.  I may well finish the first draft before the bus comes (I did).  But I don’t think I’m going to be trying to work on any fiction after that, even fiction that I had already begun.  I don’t think I could completely finish a new novel and have it ready for publication before October of this year.  I certainly wouldn’t want to work on The Dark Fairy and the Desperado, because that’s supposed to be the first of a series, so even finishing it by October would be rather beside the point.  Only Outlaw’s Mind has any chance of being done, but that’s far from certain.

And once October comes, my age will no longer be a prime number, though the latter portion of the year still will be for a few more months after that.  And I don’t want to be past my prime yet again if I can help it, because the next time I and the year will be in my prime is far too long from now to contemplate.

It’s not that riding the bus to the train and then back again is such a big deal.  Hell, I did it for a long time after getting out of work release**, and though I was tired a lot, I was thinner and more fit, certainly.

It’s amazing how things that would have been minor to moderate inconveniences way back when one had family and friends around, as well as a (misguided) sense of purpose, become just overwhelming when one has no one around from day to day, and no ability to connect with anyone, and when one is already teetering on the edge of collapse***.  Setbacks feel like mortal crises, and in a way, they are, because they really do push one to the brink of literal self-destruction, and that brink itself is not a stable platform.  It’s a cliff ledge over an abyss, and it’s riddled with cracks, more and more all the time, and it could give way any second, at the slightest perturbation.

Ugh, all this heavy-handed use of metaphor is galling.  I feel as if I’m trying to be evasive or something, as though I can’t say clearly what I mean without making things worse.  I guess my point is merely that I have nothing to which to look forward, I am achieving nothing and contributing nothing, I have lost almost everything that mattered to me, as well as pretty much all the skill I’d ever had at connecting to other people, and so I have no local, day-to-day emotional support nor any ability or clue about how to achieve it.

Even when people try to reach out to me, I react defensively; I find such situations stressful and even frightening at some level, like a feral cat that can’t be approached even when someone is giving it food.  It’s difficult to trust other people after a certain point.  If nothing else, prison can do that to you.  I even tend to say now that I don’t trust anyone, and even that I don’t believe in trust, I just take calculated risks.  I’m not lying when I say that; it’s really the way I think.

It’s all just so tiring and thoroughly unfulfilling.  And it’s not as though my chronic pain has stopped, even though I don’t write about it often.  It’s been going on for twenty years already; why would it suddenly stop?  That’s just now how significant biological damage works, especially neurological damage.

Anyway, the point is, I’m getting fed up and worn out, and things are more or less entirely pointless to me, as I suppose they have been for a long time.  I’m 53 and the year is ’23, which are both prime numbers.  Today isn’t a prime number day of the month, but there are 7 more such days left in January…and seven is a prime number itself!  That’s nice.

I’m just about out of gas.

But like I said, I hope you’re all feeling much better than I am.  If not, the world is even worse than I thought it was, and that’s saying something.

*I was correct in his assessment.  The northbound bus arrived at the time I had been expecting, incorrectly, to catch the southbound one.  The situation makes sense.  The intersection at which I was waiting was near the south end of the bus route, so it was near the beginning for the northbound, but near the end for the southbound.

**In fact, I feel almost as though I’m regressing back to my earlier state.  Maybe I should just arrange to do something so that I go back to prison.  But that is a pain.  There are good things about prison, but the inconvenience is irritating.

***It’s funny, on Saturday my brother texted just to ask how I was doing, and I replied that I was metastable at least‒an unusually effusive report for me, but more accurate than I knew.  Those of you familiar things like energy diagrams for quantum fields and for chemical reactions and for other similar systems will recognize that something that is metastable is a system that will stay in its current state if undisturbed‒it’s on or near some plateau of the energy function‒but if nudged at all will fall down the slope of the energy curve.  Imagine a pencil perfectly balanced on it’s tip.  If nothing disturbs it in any way, it could stay that way forever.  But if even a slight breeze comes along, it will topple.  I feel that, if I’m not indeed already toppled, or toppling, then I’ve barely been able to retain my balance on my pencil point.  I don’t think I can keep it up much longer.

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Some thoughts (on an article) about Alzheimer’s

I woke up very early today‒way too early, really.  At least I was able to go to bed relatively early last night, having taken half a Benadryl to make sure I fell asleep.  But I’m writing this on my phone because I had to leave the office late yesterday, thanks to the hijinks of the usual individual who delays things on numerous occasions after everyone else has gone for the day.  I was too tired and frustrated to deal with carrying my laptop around with me when I left the office, so I didn’t.

I’m not going to get into too much depth on the subject, but I found an interesting article or two yesterday regarding Alzheimer’s disease.  As you may know, one of the big risk factors for Alzheimer’s is the gene for ApoE4, a particular subtype of the apolipoprotein gene (the healthier version is ApoE3).  People with one copy of the ApoE4 gene have a single-digit multiple of the baseline, overall risk rate for the disease, and people with 2 copies have a many-fold (around 80) times increased risk.

It’s important to note that these are multiples of a “baseline risk” that is relatively small.  This is a point often neglected when discussing the relative risks of a disease affected by particular risk factors when such information is conveyed to the general public.  If the baseline risk for a disease were one in a billion (or less), then a four-times risk and an eighty-times risk might be roughly equivalent in the degree of concern they should raise.  Eighty out of a billion is still less than a one in ten million chance for a disease; some other process would be much more likely to cause one’s deterioration and demise rather than the entity in question.

However, if the baseline risk were 1%‒a small but still real concern‒then a fourfold multiplier would increase the risk to one in 25.  This is still fairly improbable, but certainly worth noting.  An eighty-fold increase in risk would make the disease far more likely than not, and might well make it the single most important concern of the individual’s life.

Alzheimer’s risk in the general population lies between these two extremes, of course, and that baseline varies in different populations of people.  Some of that variation itself may well be due to the varying frequency of the ApoE4 gene and related risk factors in the largely untested population, so it’s tricky to define these baselines, and it can even be misleading, giving rise to false security in some cases and inordinate fear in others.  This is one example of how complex such diseases are from an epidemiological point of view, and highlight just how much we have yet to learn about Alzheimer’s specifically and the development and function of the nervous system in general.

Still, the article in question (I don’t have the link, I’m sorry to say) concerned one of the functions of the ApoE gene (or rather, its products) in general, which involve cholesterol transport in and around nerve cells.  Cholesterol is a key component of cell membranes in animals, and this is particularly pertinent in this case because the myelin in nerves is formed from the sort of “wrapped up” membranes of a type of neural support cell*.

cns myelin

This particular study found that the cells of those with ApoE4 produced less or poorer myelin around nerve cells in the brain, presumably because of that faulty cholesterol transport, and that the myelin also deteriorated over time.

Now, the function of myelin is to allow the rapid progression of nerve impulses along relatively long axons, with impulses sort of jumping from one space (a “Node of Ranvier”) between myelin sheath and another rather than having to travel all the way down the nerve, which a much slower process, seen mostly in autonomic nerves in the periphery.  When normally myelinated nerves lose their myelin, transmission of impulses is not merely slowed down, but becomes erratic and often effectively non-existent.

myelin in general

The researchers found that a particular pharmaceutical can correct for at least some of the faulty cholesterol transport and can thereby support better myelin survival.  Though this does not necessarily point toward a cure or even a serious disease-altering treatment over the long term, it’s certainly interesting and encouraging.

But of course, we know Alzheimer’s to be a complex disease, and it may ultimately entail many processes.  For instance, it’s unclear (to me at least) how this finding relates to the deposition of amyloid plaques, which are also related to ApoE, and are extracellular findings in Alzheimer’s.  Are these plaques the degradation products of imperfect myelin, making them more a sign than a cause of dysfunction, or are they part of the process in and of themselves?

Also, it doesn’t address the question of neurofibrillary tangles, which are defects found within the nerve cells, and appear to be formed from aggregates of microtubule-associated proteins (called tau protein) that are atypically folded and in consequence tend to aggregate and not to function and to interfere with other cellular processes, making them somewhat similar to prions**.  It’s not entirely clear (again, at least to me) which is primary, the plaques or the tangles, or if they are both a consequence of other underlying pathology, but they both seem to contribute to the dysfunction that is Alzheimer’s disease.

So, although potential for a treatment that improves cholesterol transport and supports the ongoing health of the myelin in the central nervous systems of those at risk for Alzheimer’s is certainly promising, it does not yet presage a possible cure (or a perfect prevention) for the disease.  More research needs to be done, at all levels.

Of course, that research is being undertaken, in many places around the world.  But there is little doubt that, if more resources were to be put into the study and research of such diseases, understanding and progress would proceed much more quickly.

The AIDS epidemic that started in the 1980s was a demonstration of the fact that, when society is strongly motivated to put resources into a problem, thus bringing many minds and much money to the work, progress can occur at an astonishing rate.  The Apollo moon landings were another example of such rapid progress.  Such cases of relative success can lead one to wonder just how much farther, how much faster, and how much better our understanding of the universe‒that which is outside us and that which is within us‒could advance if we were able to evoke the motivation that people have to put their resources into, for instance, the World Cup or fast food or celebrity gossip.

I suppose it’s a lot to expect from a large aggregate of upright, largely fur-less apes only one step away from hunting and gathering around sub-Saharan Africa that they collectively allocate resources into things that would, in short order, make life better and more satisfying for the vast majority of them.  All creatures‒and indeed, all entities, down to the level of subatomic particles and up to the level of galaxies‒act in response to local forces.  It’s hard to get humans to see beyond the momentary impulses that drive them, and this shouldn’t be surprising.  But it is disheartening.  That, however, is a subject for other blog posts.

I’ll try to have more to say about Alzheimer’s as I encounter more information.  Just as an example, in closing, another article I found on the same day dealt with the inflammatory cells and mediators in the central nervous system, and how they can initially protect against and later worsen the problem.  We should not be too surprised, I suppose, that a disease that leads to the insidious degeneration of the most complex system in the known universe‒the human brain‒should be complicated and multifactorial in its causation and in its expression.  This should not discourage us too much, though.  The most complicated puzzles are, all else being equal, the most satisfying ones to solve.

*The cell type that creates myelin in the peripheral nervous system (called Schwann cells) is different than the type that makes it in the central nervous system (oligodendrocytes), and this may be part of why Alzheimer’s affects the central nervous system mainly, whereas diseases like ALS (aka Lou Gehrig’s Disease), for instance, primarily affect the nervous system outside the brain.

**The overall shape of a protein in the body is a product of the ordering of its amino acids and how their side chains interact with the cellular environment‒how acidic or basic, how aqueous or fatty, how many of what ions, etc.‒and with other parts of the protein itself.  Some proteins can fold in more than one possible way, and indeed this variability is crucial to the function of proteins as catalysts for highly specific chemical reactions in a cell.  However, some proteins can fold into more than one, relatively stable form, one of which is nonfunctional.  In some cases, these non-functional proteins interact with other proteins of their type (or others) to encourage other copies of the protein to likewise fold into the non-functional shape, and can form polymers of the protein, which can aggregate within the cell and resist breakdown, sometimes forming large conglomerations.  These are the types of proteins that cause prion diseases such as “mad cow disease”, and they appear also to be the source of neurofibrillary tangles in people with Alzheimer’s disease.

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You’ve got some nerve!

It’s Saturday, the 19th of November in 2022, and I’m going in to the office today, so I’m writing a blog post as well.  I’m using my laptop to do it, and that’s nice—it lets me write a bit faster and with less pain at the base of my right thumb, which has some degenerative joint disease, mainly from years of writing a lot using pen and paper.

The other day I started responding to StephenB’s question about the next big medical cure I might expect, and he offered the three examples of cancer, Alzheimer’s and Parkinson’s Disease.  I addressed cancer—more or less—in that first blog post, which ended up being very long.  So, today I’d like to at least start addressing the latter two diseases.

I’ll group them together because they are both diseases of the central nervous system, but they are certainly quite different in character and nature.  This discussion can also be used to address some of what I think is a dearth of public understanding of the nature of the nervous system and just how difficult it can be to treat, let along cure, the diseases from which it can suffer.

A quick disclaimer at the beginning:  I haven’t been closely reading the literature on either disease for quite some time, though I do notice related stories in reliable science-reporting sites, and I’ll try to do a quick review of any subjects about which I have important uncertainties.  But if I’m out of date on anything specific, feel free to correct me, and try to be patient.

First a quick rundown of the two disorders.

Alzheimer’s is a degenerative disease of the structure and function of mainly the higher central nervous system.  It primarily affects the nerves themselves, in contrast to neurologic diseases that interfere with supporting cells in the brain*.  It is still, I believe, the number one cause of dementia** among older adults, certainly in America.  It’s still unclear what the precise cause of Alzheimer’s is, but it is associated with the development of “cellular atypia made of what are called “neurofibrillary tangles” within the cell bodies of neurons, and these seem to interfere with normal cellular function.  To the best of my knowledge, we do not know for certain whether the plaques are what directly and primarily cause most of the disease’s signs and symptoms, or if they are just one part of the disease.  Alzheimer’s  is associated with gradual and steadily worsening loss of memory and cognitive ability, potentially leading to loss of one’s ability to function and care for oneself, loss of personal identity, and even inability to recognize one’s closest loved ones.  It is degenerative and progressive, and there is no known cure and there are few effective treatments that are not primarily supportive.

Parkinson’s Disease (the “formal” disease as opposed to “Parkinsonism”, which can have many causes, perhaps most notably the long-term treatment of psychiatric disorders with certain anti-psychotic medicines), is a disorder in which there is loss/destruction of cells in the substantia nigra***, a region in the “basal ganglia” in the lower part of the brain, near the takeoff point of the brainstem and spinal cord.  It is dense with the bodies of dopaminergic neurons, which there seem to modulate and refine motor control of the body.  The loss of these nerve cells over time is associated with gradual but progressive movement disorders, including the classic “pill-rolling” tremor, shuffling gait, blank, mask-like facial expression, and incoordination with tendency to lose one’s balance.  There are more subtle and diffuse problems associated with it, including dementia and depression, and like Alzheimer’s it is generally progressive and degenerative, and there is no known “cure”, though there are treatments.

Let me take a bit of a side-track now and address something that has been a pet peeve of mine, and which contributes to a general misunderstanding of how the nervous system and neurotransmitters work, and how complex the nature and treatment of diseases of the central nervous system can be.  This may end up causing this blog post to require at least two parts, but I think it’s worth the diversion.

I mentioned above that the cells of the substantia nigra are mainly dopaminergic cells.  This means that they are nerve cells that transmit their “messages” to other cells mainly (or entirely) using the neurotransmitter dopamine.  The term “dopaminergic” is a combination word, its root obviously enough being “dopamine” and its latter half, “ergic” relating to the Greek word “ergon” which means to do work.  So “dopaminergic” means those cells do their work using dopamine, and—for instance—“serotonergic” refers to cells that do their work using serotonin.  That’s simple enough.

But the general public seems to have been badly educated about what neurotransmitters are and do; what nerve impulses are and do; and what the nature of disorders, like for instance depression, that involve so-called “chemical imbalances” really entails.

I personally hate the term chemical imbalance.  It seems to imply that the brain is some kind of vat of solution, perhaps undergoing some large and complex chemical reaction that acquires some mythical state of equilibrium when it’s working properly, but when, say, some particular reactant or catalyst is present in too great or too small a quantity, doesn’t function correctly.  This is a thoroughly misleading notion.  The brain is an incredibly complex “machine” with hundreds of billions of cells interacting in extremely complicated and sophisticated ways, not a chemical reaction with too many or too few moles on one side or another.

People have generally heard of dopamine, serotonin, epinephrine, norepinephrine, and the like, and I think many people think of them as related to specific brain functions—for instance, serotonin is seen as a sort of “feel good” neurotransmitter, dopamine as a “reward” neurotransmitter, epinephrine and norepinephrine as “fight or flight” neurotransmitters, and so on.

I want to try to make it very clear:  there’s nothing inherently “feel good” about serotonin, there’s nothing inherently “rewarding” about dopamine, and—even though epinephrine is a hormone as well as a neurotransmitter, and so can have more global effects—there’s nothing inherently “fight or flight” about the “catecholamines” epinephrine and norepinephrine.

All neurotransmitters—and hormones, for that matter—are just complex molecules that have particular shapes and configurations and chemical side chains that make them better or worse fits for receptors on or in certain cells of the body.  The receptors are basically proteins, often combined with special types of “sugars” and “fats”.  They have sites in their structures into which certain neurotransmitters will tend to bind—thus triggering the receptor to carry out some function—and to which other neurotransmitters don’t bind, though, as you may be able to guess from looking at their somewhat similar structures, there can be some overlap.

dopamine

Dopamine

serotonin

Serotonin

epinephrine

Epinephrine

Neurotransmitters are effectively rather like keys, and their functions—what they do in the nervous system—are not in any way inherent in the neurotransmitter itself, but in the types of processes that get activated when they bind to receptors.

There is nothing inherently “rewarding” about dopamine, any more than there is anything inherently “front door-ish” to the key you use to unlock the front door of your house, or “car-ish” to the keys that one uses to open and turn on cars.  It’s not the key or the lock that has inherent nature, it’s whatever function is initiated when that key is put into that lock, and that function depends entirely on the nature of the target.  The same key used to open your door or start your car could, in principle, be used to turn on the Christmas lights in Rockefeller Center or to launch a nuclear missile.

Dopamine is associated with areas of the nervous system that function to reward—or more precisely, to motivate—certain behaviors, but it is not special to that function.  As we see in Parkinson’s Disease, it is also used in regions of the nervous system involved in modulating motor control of the body.  The substantia nigra doesn’t originate the impulses for muscles to move, but it acts as a sort of damper or fine tuner on those motor impulses.

Neurotransmitters work within the nervous system by being released into very narrow and tightly closed spaces between two nerve cells (a synapse), in amounts regulated by the rate of impulses arriving at the bulb of the axon.  Contrary to popular descriptions, these impulses are not literally “electrical signals” but are pulses of depolarization and repolarization of the nerve cell membrane, involving “voltage-triggered gates****” and the control of the concentration of potassium and sodium ions inside and outside the cell.

synapse

A highly stylized synapse

The receptors then either increase or decrease the activity of the receiving neuron (or other cell) depending on what their local function is.  It’s possible, in principle, for any given neurotransmitter to have any given action, depending on what functions the receptors trigger in the receiving cell and what those receiving cells then do.  However, there is a fairly well-conserved and demarcated association between particular neurotransmitters and general classes of functions of the nervous system, due largely to accidents of evolutionary history, so it’s understandable that people come to think of particular neurotransmitters as having that nature in and of themselves…but it is not accurate.

Okay, well, I’ve really gone off on my tangents and haven’t gotten much into the pathology, the pathophysiology, or the potential (and already existing) treatments either for Parkinson’s or Alzheimer’s.  I apologize if it was tedious, but I think it’s best to understand things in a non-misleading way if one is to grasp why it can be so difficult to treat and/or cure disorders of the nervous system.  It’s a different kind of problem from the difficulties treating cancer, but it is at least as complex.

This should come as no surprise, given that human nervous systems (well…some of them, anyway) are the most complicated things we know of in the universe.  There are roughly as many nerve cells in a typical human brain as there are stars in the Milky Way galaxy, and each one connects with a thousand to ten thousand others (when everything is functioning optimally, anyway).  So, the number of nerve connections in a human brain can be on the order of a hundred trillion to a quadrillion—and these are not simple switching elements, like the AND, OR, NOT, NAND, and NOR gates for bits in a digital computer, but are in many ways continuously and complexly variable even at the single synapse level.

When you have a hundred trillion to a quadrillion more or less analog switching elements, connecting cells each of which is an extraordinarily complex machine, it shouldn’t be surprising that many things can go wrong, and that figuring out what exactly is going wrong and how to fix it can be extremely difficult.

It may be (and I strongly suspect it is the case) that no functioning brain of any nature can ever be complex enough to understand itself completely, since the complexity required for such understanding increases the amount and difficulty of what needs to be understood*****.  But that’s okay; it’s useful enough to understand the principles as well as we can, and many minds can work together to understand the workings of one single mind completely—though of course the conglomeration of many minds likewise will become something so complex as likely to be beyond full understanding by that conglomeration.  That just means there will always be more to learn and more to know, and more reasons to try to get smarter and smarter.  That’s a positive thing for those who like to learn and to understand.

Anyway, I’m going to have to continue this discussion in my next blog post, since this one is already over 2100 words long.  Sorry for first the delay and then the length of this post, but I hope it will be worth your while.  Have a good weekend.

*For instance, Multiple Sclerosis attacks white matter in the brain, which is mainly long tracts of myelinated axons—myelin being the cellular wraparound material that greatly speeds up transmission of impulses in nerve cells with longish axons.  The destruction of myelin effectively arrests nerve transmission through those previously myelinated tracts.

**“Dementia” is not just some vague term for being “crazy” as one might think from popular use of the word.  It is a technical term referring to the loss (de-) of one’s previously existing mental capacity (-mentia), particularly one’s cognitive faculties, including memory and reasoning.

***Literally, black substance.

****These are proteins similar to the receptors for neurotransmitters in a way, but triggered by local voltage gradients in the cell membrane to open or close, allowing sodium and/or potassium ions to flow into and out of the cell, thereby generating more voltage gradients that trigger more gates to open, in a wave that flows down the length of the axon, initially triggered usually at the body of the nerve cell.  They are not really in any way analogous to an electric current in a wire.

*****You can call that Elessar’s Conjecture if you want (or Elessar’s Theorem if you want to get ahead of yourself), I won’t complain.