Saturday, January 24, 2015

Chapter One - Neuroanatomy 101



This will be a very basic primer into neuroanatomy.

And it will give us some insight into what makes a brain - IE: "you" - tick. It will seem quite lengthy, for which I apologize, but there is a lot to get to. If we are to begin better understanding our complex selves - or even our simple selves - it is basic brain functions as understood by current neuroscience that we need to better understand and be aware of. It is my hope that this post will serve as a) a reference for us to refer back to as we go along, b) a reference for your future use and more importantly, c) an impetus and inspiration for further curiosity and reading on your part (if not, I will be doing my best to provide as comprehensive an understanding as possible in the easiest way for us layman to utilize).

So here we go, let's dive in.

First of all, you have in the neighbourhood of eighty-six billion of these:





That's a neuron and according to renowned neuroscientist David Eagleman, each one - all eighty-odd billion of 'em - is as complicated as a major city (there's an astonishing level of activity that happens in all of your cells, it's just that brain cells take that to a new level). Neurons "encode" stuff. The details of all your thoughts, memories and all your knowledge are encoded in various neurons (for example, there's a "Jennifer Aniston neuron". Honest! The discovery of this is detailed in neuroscientist Sebastian Sueng's book, The Connectome. Whether you have a "Jen neuron" (or any such specialized bit of encoded information) or not depends, of course, on whether you've seen her (or any such person) or not and whether certain brain circuits have "decided" if this person is important to you or not). They pass that encoded stuff along (to assemble bigger pictures or ideas or memories) to other neurons via these:



Those are axons (sending) and dendrites (receiving), AKA "the wiring". Axons are what make up white matter in the brain - see more below). While brain cells tend to be more (though not completely) permanent, the finer aspects of the wiring is not. Critical connections called dendrites and synapses grow and "prune back" all the time, creating new connections (and thus new memories, learned behaviour and the such) or trimming them back (if a certain memory function falls into disuse for example). As you can see by the number of dendrites, there are many, many connections between neurons (as many as ten thousand per neuron according to some counts!). Dendrites and these multiple, multiple connections are a big part of our mental puzzle. A more realistic depiction of what these connections look like appears like this:





That bright green blob in the centre of the image is a neuron. Yup, you've got close to ninety billion of those, each one with enough activity within it to be compared to a major city. Imagine the activity of billions of cities going on in your brain (though not exactly all at once).

Communication between neurons is sent along the axons in electrical pulses not unlike Morse code. Whether that "Morse code" is sent or not depends on something called action potential, a complicated bit of business which can be boiled down to whether a given neuron or set of neurons reaches a certain threshold of excitement that makes it pass on its message.

At the point of connection between an axon and a dendrite we have a synapse and at this point the electrical pulse triggers the release of a neurochemical which will pass the message from axon to dendrite and thus onto the next neuron. The details of this transfer, and the synapse itself, look something like this:




This happens to be for the system involving the neurotransmitter dopamine. You may notice opiate receptors as well, along with endorphins. There are receptors, "uptake pumps", there's a system - not shown - for whisking away excess neurotransmitter material and so on. This operates on a ridiculously delicate balance (we look at this in more detail in the post on the dopamine pathways and serotonin pathways ). There are something like one hundred known neurotransmitters, all of which perform inter-neuron communication in various regions of the brain and all of which are responsible for various functions that drive "you".


Look again at that tiny detail. Much of who you are and what you do, not to mention all your memories (some theories on long term memories posit that memories exist in our synapses), depends on that infinitesimally small chemical transaction. Now get this; it is estimated that your brain has somewhere over one hundred and fifty trillion synaptic connections at any one time all performing those little chemical transactions. And to put that number in perspective, in just a few cubic centimeters of cortical tissue you have more synaptic connections than there are stars in the Milky Way (David Eagleman's Incognito).


Neurotransmitters are the main focus of pharmacological psychiatry so we'll be revisiting what goes on here in more detail in future posts (see the above two posts on dopamine and serotonin).

The dopamine system and pathways happen to be one of the most studied and well understood and it is also widely implicated in schizophrenia and bipolar disorder (and many addictive behaviours as it turns out). The dopamine pathway looks roughly (and I do mean roughly) like this:





As you can see, there are all kinds of key brain regions included in the loop. And what's this? Our "planning and judgement" centre is a destination? Yuppers. A lot of what you "think" is "good planning and judgement" may well be just your primitive brain reward system sending an emotion generated "good feeling" message to your "command centre". And this diagram just represents the dopamine pathway. Remember, there are over a hundred different neurotransmitters at work throughout your brain all governing - way below your conscious control - various functions going on in all those billions of cities in your brain.

Let's return to the "wiring". There's "local" and "long distance" wiring. Local wiring in the mammalian neocortex looks something like this (and this is a greatly simplified drawing). It works in layers and each layer performs a slightly different level of function (from Sebastian Seung's The Connectome).



Long distance wiring is longer axons that form "bundles" (the white matter mentioned above). This wiring connects the different brain regions. It is believed by some neuroscientists, such as Sebastian Seung (linked to above), that it is the unique wiring we each have between our brain regions - or "connectome" - that is responsible for much of "who we are". A basic "wiring harness" looks something like this:








The brain and its wiring is not, as once thought, "set" once full neurological adulthood is reached (about age 25). As mentioned, axons and dendrites grow and prune back depending on the demands, or lack of them, put on a region at any one time. This falls under the general heading of neuroplasticity, a term that describes the malleability and changeability of our finest (and we're talking very fine) and even major brain structures.


No two "wiring harnesses" or connectomes in people will be alike. They will form differently from birth and individual life experiences and environments will alter the course of their development throughout life. There is mounting evidence that differences in white matter connections - these "wiring bundles" - may play major roles in many psychiatric disorders.


I introduce and talk more about neuroplasticity in this post, but for now it's important to know that this plasticity can be good (the brain changing to adapt to a major change such as blindness) or bad (adapting to a harmful behaviour or practice (brought on usually through negative experiences or environmental conditions)). And that wiring? You have, in that small space between your ears, enough wiring to wrap around the world - twice.

Aside from "direct wiring", we also have various brain wave oscillations that appear to play important roles in producing or attaining certain states of consciousness, sleep activity, memory consolidation and more. These have very Greek names like Theta, Delta, Beta, Alpha and Gamma. We can think of brain wave oscillations as a sort of "wifi" in the brain that allows more instantaneous and widespread communication and cooperation between distant brain regions. Imagine it like being at a rave with strong pulsating electro-pop music pounding through the speakers and thousands of individual minds all tuning into that frequency and moving in unison. It's also been proposed that our highly (and unique among the animal world) pre-frontal cortex uses these "neural rhythms" like a "quarterback" to direct and coordinate activity in the brain.


Back to the wiring, it does not end in the brain of course. The wiring includes the central nervous system and connects every square centimeter of your body to your brain, something like this:




and this:




These are not only to send messages to muscles to move and to receive information in return or to receive and send pain signals (and we'll learn that this is a two way street) but are also part of a "full systems" monitoring program that is constantly testing what's going on in, as the latter diagram shows, your major organs. We'll be examining this in more detail as well when we learn more about the mind-body connection and how, for example, what goes on in your stomach may affect your mental health. For that matter, what goes on anywhere in your body is going to affect your brain in some way.

Aside from neurotransmitters, there are also hormones involved, such as the stress hormone cortisol. Its pathway looks something like this:




The stress response system is based on our primitive brain "fight or flight" response to perceived danger (and the term "perceived" is very pertinent here. How we perceive danger is one of the things that gets out of wack in our brains outside of our conscious control. Phobias fall under this category, among many others including anxiety disorders, depression and even schizophrenia). This system is essential to our survival but what's important to understand now is that this system evolved for fairly simple dangers like a saber-toothed tiger eyeing you for dinner. In our modern wacky world the concept of "danger" and our response to that is way, way more complicated and this system is often put under extreme duress and it is during situations of extreme duress that many mental health problems arise.

I cannot overstate the importance of the stress response system when considering both acute or chronic mental health disorders or situations. I introduce the stress response system in this post and that will eventually be a four or five part series as we try to understand this system's enormous effect on our behaviours and reactions along with our physical and mental health.

There are of course numerous hormones that greatly influence our behaviours and "who we are". Some are quite familiar to most of you - testosterone and estrogen for example - but we'll look at others as well and more importantly look at better understanding the roles these play in what we do and why we do them (or not do certain things).

And in among all those neurons and wiring are glia cells. Neuroscience only recently began discovering the enormous importance of these "support cells". Once thought only to be supporting cells in a literal sense (like scaffolding), it is now known that glia cells - microglia, astrocytes and oligodenrocytes - play absolutely essential roles in all aspects of neuronal communications. One critical role is in supporting the growth of the myelin sheath, a protective coating on axons (the breakdown of myelin is thought to play a role in MS). When we look at neuroplasticity, we'll learn more about the enormous role synaptic formation and pruning plays in memory and learning functions and glia cells are a vital fundamental part of this process. As well, they are involved in supplying nutrients and oxygen to neurons along with various "clean up" duties, whisking away toxic waste material that are produced in normal cellular function (like any cell, nutrients go in, waste comes out). Recent research suggests that among the reasons we need to sleep is that glia cells need the brain to be in a resting state for them to perform many of their functions (most critically, it appears, the essential house cleaning duties they perform). Glia cells look something like this:



Isn't this just the funnest stuff?! I love this stuff! Let's carry on.

Reptile brains, then higher brains followed by the mammalian brain, then the early hominid brains and finally the modern human brain evolved over millions of years. It is impossible to know precisely how these different regions evolved, of course, and I cannot report a lot of agreement in the evolutionary neuroscience community on this but what is clear today is the three distinct regions, all with different structuring and functions. We have the brain stem at the bottom, then the limbic region and - for our purpose here for understanding modern humans - the mammalian and humanoid outer cortex. Thus our basic brain outline looks like this:




That big (and ancient in evolutionary terms) blob at the back of the brain is the cerebellum. That's where body movements are coordinated, where your abilities of balance and body posture are held and equilibrium is controlled (and more recent research shows that it is involved in coordination of many higher cognitive mental activities, most notably, musical abilities). If you're not super graceful, blame this region, not yourself. The limbic system is where a number of major control centres reside, including, but not limited to, the aforementioned amygdala, the hypothalamus (the control centre for many autonomic functions), the hippocampus (involved in memory forming, organization and storing) and the basal ganglia (or basal nuclei; involved with a variety of functions, including voluntary motor control, procedural learning related to routine behaviours or "habits" such as bruxism, eye movements, cognitive and emotional functions).

Better understanding how these major regions control who you are and your outward behaviour and decision making processes is going to be a big focus of our exploration of mental health and behavioual issues.

Finally, we have the neocortex. If you have browsed articles on the brain you'll likely have come across mention of various "lobes". these are the four major regions and are outlined as thus:



Starting from the right, the back of the brain, we have the occipital lobe. That, incidentally, is actually where you "see". Our eyes merely collect light. That live action movie show that takes place when you open your eyes gets produced, edited (yes, whatever you may think, a lot of editing takes place of what your eyes take in) and assembled mostly in your occipital lobe and which then presents the final cut to "you".


Above and to the front of the occipital lobe there is the parietal lobe which is mostly concerned with processing sensory information. Mid brain, roughly around our ears, is the temporal lobe. This is where the processing of auditory information takes place (where you "hear") and is also very crucial in working with the hippocampus and amygdala in long term memory formation. As sight and sound must work very close together in producing that "live picture show" we live in every day, there is a great deal of cooperative work between the temporal and occipital lobes.

Those areas will all be very similar among all mammals. Moving to the very front of the brain we have the rather aptly named frontal lobe. This, folks, is where the rubber meets the road in better understanding human (and our) behaviours and "issues". For it is here where most of what we think of as "we" - our humanness - is housed, specifically in an area right at the front of this lobe called the prefrontal cortex (right above and behind our eyes).

The neocortex is where the responsibilities of our higher cognitive functions lie. This is a short list but all areas of thought and cognitive functions will have a key corresponding group of neurons that will be involved in that function. that looks roughly (and again, I do mean roughly) like this:




These represent just a small handful of examples and are only roughly located in this diagram as the areas are presently understood (neuroscience is making new discoveries all the time so none of the exact specifics of these locations are set in stone but the basics are well understood and agreed upon). How "good" you are at any particular activity will basically depend on a) how well developed a particular region is (say the Brodmann and Wernicke areas of language, for example (roughly "speech production" on the chart) or something more rudimentary like your cerebellum as we saw), b) how well the wiring is developed between your regions and c) how your particular neurochemical pathways perform.

That our brain regions and the connections between them (the "connectome" mentioned and illustrated above) are all different puts a whole new meaning on "smart" or "talented". "Smart" or "talented" is just a blessing of various regions being better proportioned and wired for a given task and you accidentally discovering the use of these regions (or more likely having them discovered for you). If you're a math "genius" and make a living from that, for example, you can climb down off your high horse and thank your lucky stars that you were gifted (and we'll see what "gifted" really means ... nothing to do with "you" I can assure you) with highly developed regions specific to math tasks (nature) and that they were discovered and developed (nurture, which strengthens the connections, or wiring, between these regions and the rest of your brain). Many people may be similarly gifted but tragically never discover these gifts. Others may not be so gifted but are cursed with high desire (or being driven by well meaning but ill-advised parents) and thus tragically beat their heads against the wall (and beat up on themselves) trying to do something they were simply not endowed to do. This is very important in understanding "who we are" and why are that way.


What almost anyone will know is that the brain is divided into two hemispheres:




Unfortunately, what most people have been taught or have learned about brain hemispheres and their respective functions is myth. While it is true that each hemisphere handles different tasks and controls different functions, it is only recently that it has been learned in modern neuroscientific research that the coordination between the hemispheres and specific "task sharing" is vastly more complex than previously understood. This alone is an enormous topic so all I can ask is for you to put aside probably the great majority of what you understand about brain hemispheres in the modern human brain.

All of this, the billions of neurons, the trillions of synapses, the dozens and dozens of specific brain regions, the hundreds of thousands of kilometres of wiring that tie it all together and the more than one hundred neurotransmitters, hormones and proteins that make it all communicate, harmonize to make up this - your brain:





The brain from any healthy adult will look like the one pictured above but here's something to consider, and is the essential foundation to what we will learn about brains - no two brains are alike. They are as unique as fingerprints. All those regions are connected slightly differently between us as well as some regions being better developed or activated and some not so much (which can be long term or short term), the wiring is slightly different between us and so on. This is, as I've pointed out, determined by genetics and environmental factors, with a strong emphasis on environmental factors. Even identical twins (of which I am one) who start out genetically identical will develop quite different brains (as a twin myself, and because twin studies are so fascinating, we'll try to get to twin studies at some point).


The brain collects "data" through the five senses - sight, sound, taste, touch and smell (and we now know that there is a critical and major "sixth" sense - our gut-brain connection) - runs this data through various brain regions and create the "reality" we perceive in our minds. Because our sensory organs and brains are all genetically different (with the exception of twins) plus are wired and developed slightly differently, we will all have different "versions" of "reality". This is why we find it hard to agree even when we're both looking at the exact same thing (like two people seeing a spider for example. One may look on with fascination and curiosity, the other will have a phobic melt down).





This is going to be a critical part of our examination of human behaviour and the brain. Obviously our differing views of realities - and we have very, very little conscious input into what these are (or exercise very little as we'll see) - is going to create very different views of the world and thus behaviour. "Reality" is one of the great philosophical questions of all time and, as it turns out, crucial to understanding the human brain and our inward and outward "selves" and, most importantly, how all our widely varying "selves" get along with other "selves". I have many ideas, thoughts and views that it is how our brains create the "reality" that we experience that are at the root of our mental health woes. And not only that, but it may be that there's nothing really wrong with our version of reality, per se, but that it doesn't fit in with standardized models of "reality" and it is this ostracizing that creates our mental anguish.

A huge thing to understand is that all these components we've looked at run a mind boggling number of subconscious "programs", or what many in the "brain biz" refer to as "zombie programs" and it's your particular collection of these programs (we all vary in these though some are quite standard) that run "you". No, "you" don't run "you", all these automated zombie programs - programs that run through all those neurons, wiring via electrical pulses, neurochemicals and hormones (to put it very basically) - run "you". Zombie programs are all your daily routines that you don't need to think about in addition to all kinds of other little programs that push you forward through life.

All those "conscious decisions" you make are almost certainly to be the result of various zombie programs spitting out, for example, the "decision" to buy a new car (which is just a glorified modern variation on ancient hunter-gatherer instincts) or take a new night class or pick a certain supermarket product over the others and so on. Then your dopamine reward centre gives you a "hit" of happy feeling dopamine to "reward" and "re-enforce" this behaviour. Then your brain creates a post hoc inner dialog to justify or rationalize this "decision".

Learning more about these subconscious systems is going to be a huge part of our undertaking in understanding why we are the way we are and what's going wrong.

Phew! Wasn't that fun?! And that was just the very basics. In future posts we'll look at most of these parts in more detail. We could think of all these parts as pieces of a puzzle that we are putting together. The completed puzzle is a biological computer of such dazzling complexity that human language is inadequate to completely describe it. For every second of every moment you are alive, your biological computer - your brain - will be performing an astounding number of functions, virtually all of which are outside of your conscious awareness, let alone control. In fact, as I've already alluded, we will see how astonishingly little control we have over who we are and what we do (though once we understand why that is it'll be far less astonishing and the only way we could possibly operate and get through life).


But perhaps more importantly, we'll learn more about just what kind of control we do have. And this is going to be where "the rubber meets the road" in this blog - learning better how to control your amazing and beautiful brain.

I promise that not all posts are going to be so science based and detailed. But in order for you to understand what's really going on in you and more importantly how to change it, being familiar with at least some of the basics of what's "under your hood" is very useful. So we're going to slog through more similar posts examining things in more detail. I will do my best to make it fun, though.

And I promise, there will be no tests so don't worry about memorizing all of that. :)

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