Thursday, February 25, 2016

Neurochemical in Focus - Dopamine




Way, way, way back in Neuroanatomy 101 I briefly mentioned neurotransmitters and the neurotransmitter dopamine (pronounced DOUGH-pah-mean). I've also written about dopamine in my other blog in a post called Dopamine the Bus Driver (which was a very popular post among my neuroscience and brain nerd buds back in its day, or at least among those who liked fun ways of explaining something complex) and it came to me this morning that it was about time we had a closer look at neurotransmitters like I had promised.

As I've talked about ad nauseum, whatever it is we are experiencing, or are able to do or not do, or all of our behaviours good or bad, compulsive, impulsive or planned, all of our thoughts and emotions and motivations, everything - in other words - about "you" and who and what you are, even your very soul - is all one hundred percent created by the unfathomably complex biological organism that is our brain. So when we want to know what's going on when we are experiencing difficulty or witnessing someone else who is, it is understanding how our brains work where the answers lie. Which is why I am so motivated to study neuroscience and then - tada! - crunch all the complicated stuff down into something that makes sense to mental health suffering peeps following this blog and those who want to know how to get themselves to move forward. 

The brain does a lot of things as it hums away 24/7 from not long after conception to not long after you draw your last breath, all of which requires communication of one kind or another among the eighty-six billion or so neurons you have and among the hundreds of small and large individual and highly specialized regions that must be coordinated to produce "you" and guide you through life. There are several different modes of communication and coordination that the brain utilizes but today we're going to look at the critical and essential role of neurotransmitters or neurochemicals (so called because a) they help to transmit information and b) they are relatively straight forward chemicals). 

Now we could spend forever poking around among the astronomically (sort of literally) complicated brain looking for answers out of countless (almost literally) possibilities, but today we're just going to examine dopamine because a) it is one of the best understood neurotransmitters and b) its role in our moods and behaviours is probably most pertinent to us long suffering mental health peeps. 

To be clear up front, I am not saying that what we look at here today is the thing with, for example, a particularly entrenched or "treatment resistant" case of depression but it is, as we'll see, a very important aspect to understand, consider and ultimately work at.

There are a number of things about neurochemicals that are vitally important to understanding a good number of other things we're eventually going (or have already started) to look at as well - such as memory function, brain fatigue and cognitive difficulties, neuroplasticity and the stress response system among others - so I thought this morning that it was high time we got to this. I understand that this may all look rather intimidating to some, but we're going to set that aside, let ourselves believe that "I got this" and we'll get ourselves to a better understanding of how all this works and why it's important. 

Okay, first let's get to the why this is important part. 

There are all kinds of things us mental health peeps will be experiencing as part of whatever it is we're suffering from (my main guess would be depression, but our topic here today is also critically important to understanding bipolar disorder, schizophrenia, ADD/ADHD, and others). Whatever the case, there is a very good chance that the two main things we will be suffering are: difficulty in experiencing pleasure and being motivated, the two very things in which dopamine pathways play major roles. 

We hear a lot about "brain chemicals" and the reason for this is how the popular press has picked up on and repeated the psychiatric and pharmacological explanations for "mental illnesses" which in a nutshell is explained as "chemical imbalances". This explanation has reached virtually mythical proportions since this enticing idea first took wing back in the sixties. Unfortunately, a) there remains no conclusive proof that any mental illness is due to a chemical imbalance, b) decades of subsequent neuroscience research has revealed that all human behaviours and mental experiences are vastly more complex and involve possibly dozens of other brain functions other than "brain chemicals" alone.

And there is much more to brain function than neurons, axons, dendrites, synapses and what we're going to look at here today. There is another class of cells called glia cells that provide massively important additional support to all brain functions and human brain function would not be what it is without this very critical class of cells. 

Nonetheless, what we're going to look at and learn here - the role of neurotransmitters at the synaptic level - is unquestionably important. However, we must understand them in broader contexts and that they are only a part of a enormously complicated set of processes. 

Okay, let's now look at what neurotransmitters do. 

As mentioned, we have billions and billions of neurons. There are many kinds of neurons with many specialized jobs. Whatever their job, neurons are like infinitesimally complicated "storage devices". Regular readers will remember that whatever is stored in a neuron or a given set of neurons is useless to the "big picture" if they cannot pass on what they "know" or "want to do" to neighbouring neurons or neuronal groups and thus contribute to broader brain wide functions that create all the actions and mental experiences that make up us and what we do. The main method neurons utilize to communicate with each other is via axons and dendrites. Axons send "data packets", dendrites receive.

These look something like this:




Okay, so there are a couple of neuron cell bodies, an axon extended from one to the other, and a number of receiving dendrites. This is a highly simplified artist's rendering, of course, but it allows us to see the basic idea. In this case the neuron on the left is sending a signal, an electrical pulse is depicted going towards the receiving neuron and you can see that the axon branches out to contact many dendrites. In actuality, however, a single neuron will have many axons branching out and may have up to ten thousand such connections with neurons near and far (depending on its job(s)). Now, you can have all the wiring you want running all over the place, but without a very key "connector", nothing is going to go from one set of wires to another. No transmission will take place. 

And in the brain, those "connectors" are called synapses. 

A synapse looks something like this:



For our purposes here today we don't need to understand that in too much detail, but you can see that at the axon end of things (sending) you have little sacks of neurochemicals and on the other side of the "cleft" (that little space between the two sides, about 20 nanometers across) you have little receptors. 

Let's look at something more familiar to help us understand what synapses do. Some of you may recall what old switchboards look like and how they worked. For those of you who don't, they looked like this:



As you can see, there are wires and all kinds of possible circuit combinations. You see that thing in her hand? That's a jack. That's going to connect a wire from one circuit to another. Until that is plugged in, there's no connection or transmission of information from one party to the other. Or once it's unplugged, the connection is broken and the transmission stops. 

So we can think of a synapse as that thing in her hand, a jack of sorts. Except that in the brain, it's a two step process. First we have to create a connecting point, a jack and a socket - that's the two sides of the synapse. The second process is once the connection is made, the actual transmission of information from one party to the other will be a chemical process (which is the norm throughout animal and plant cellular structures that need to somehow communicate and coordinate). 

What happens between neurons when they want to communicate is that one will get all excited (to a point called action potential), and want to send messages to all kinds of neuron buddies near and far to get something going. Once a neuron reaches a certain level of excitement, it will send an electric impulse down its axon or axons (in what I likened before to Morse code) which will stimulate the release of the neurochemicals in the axon side of the synapse to travel to the dendrite side and thus complete the transmission - to possibly tens or hundreds of thousands of neurons! The receiving neurons in turn pass all the exciting news on to hundreds of thousands more neurons and thus big thoughts or memories and all kinds of things happen. We can think of it as like sending out a mass Twitter message to thousands of receivers. 

Your brain "just" has a few more "jack and socket" connections than that switchboard above; like several hundred trillion more. 

Okay, so that's the small end of this neurochemical business and several hundred trillion is a crazy big number, so we'd better further clarify what's going on with dopamine and break that down to size. 

Each neurochemical will have one or a few specialized communication roles (but only roles) to play that involve specific brain (and thus behaviour) functions.

Let's have a look at the broader picture of the roles dopamine play.




I chose this image because it shows serotonin as well. Serotonin has become practically a household word on account of advertising's and popular press's roles in making SSRI (selective serotonin reuptake inhibitors) based antidepressants one of the most popular drugs in the western world. This is something we must really examine more closely but we look at that in a dedicated post of its own so we're going to leave that aside for now. We'll instead focus on the left side of the illustration. There are a few key brain regions illustrated there as well that are critical to our understanding of the big picture of dopamine's roles in the brain and our behaviours so we will look at those in a wee bit more detail. 

Let's first look at some basic functions. We have (as you can see):

  • motivation
  • pleasure
  • motor function
  • compulsion 
  • perseveration 

Motivation is what keeps us driving towards a goal. When we are feeling driven, or "locked on", that's dopamine at play. It's involved in a complex signaling system that makes sure we stay locked on to that goal. Sounds great, right? Not so fast. Unfortunately, what your brain decides is a "goal" may not be in alignment with what goals are best for you. This is absolutely critical for understanding many addictive behaviours and other undesirable behaviours. More later.

Pleasure is what we feel when we achieve something that our brain considers rewarding. Like motivation, however, this could be a good thing or bad thing. Pleasurable feelings, like motivated feelings, can keep us locked on to or driven toward a task or goal in anticipation of that all delicious "reward" hit the dopamine gives us. Motivation and pleasure are intrinsically linked in what we'll call our "drives".

Motor functions are what's involved in our coordinated physical movements (both conscious and unconscious) that are in part controlled by a set of nuclei located in the limbic region called the basal ganglia. This region is connected to very important brain stem regions and the cerebral cortex. It's critical for all kinds of fine motor control functions. This area - and dopamine's roles there - are at the root of Parkinson's disease. When we look closer at the dangers of long term pharmacological treatments of various psychiatric disorders and the use of anti-psychotics, we'll learn why these are so damaging. The most commonly used class of anti-psychotics "dampen" dopamine circuitry and synaptic transmissions which can cause all kinds of havoc in the long term. 

While somewhat different, I'm going to group compulsion and perseveration together because to most observers they will appear very similar. Both refer to some sort of repeated behaviour that goes against our greater good. I'll make it quite clear why this is below. 

The dopamine pathways are a very old (as in hundreds of millions of years old) part of our brain hardware and systems. All animals have essentially the same system from reptiles up to birds to all mammals. Its role was and remains very simple - keep a creature doing something critical to its survival. Find a great source of food? Bam, a dopamine hit helps insure that the creature remembers and goes back for more. Successfully mate? Bam, a dopamine hit makes sure it remembers that and to do it again.

It is not, I'm afraid to report, for the most part much different among us members of the homo sapien species. Just more sophisticated behaviours and "goals" involved. 

And, as world renowned neurobiology and human and animal behavioural expert Robert Sapolsky has demonstrated, it's not just the "hit", it's the anticipation of the hit that keeps this system - and thus "us" - jacked up about all sorts of things both good and bad. 

For example, a mouse might be trained to pull a lever in order to get a treat. To start, it will get a treat each time it pulls the lever to condition into it the expectation of a reward (the treat). What's happening here is that dopamine pathways and (very important) feedback loops are being tuned towards associating the dopamine hit with this specific task and reward. Afterwards, the treats can be reduced to only being released every tenth time. But the mouse, once conditioned, will keep pulling on that lever until it gets the treat (and thus the big dopamine hit). It will get to the point that you can remove the treat element all together and it'll keep pulling that lever over and over and over again until it drops with exhaustion because that dopamine hit and even the anticipation of the dopamine hit keep it locked into that behaviour.

Silly mouse, right? 

Well, it seems silly until you go to Las Vegas (or any casino) and watch people sit at slot machines. They, like the mouse, will sit there pulling that lever (or press buttons in modern machines) in anticipation of a reward despite astronomical odds against that reward happening. They will eschew food, going to the bathroom, going home to their families and all kinds of other essentials for a proper life to sit at that machine and what keeps them glued there, my friends, is our dopamine reward system. "Silly" mouse indeed. At least the mouse isn't pissing away the family fortune.

Thus we can also see the connection to compulsive behaviours or perseveration. 

But laugh not. Many if not most people will have similar "dopamine kick" addictions. Or compulsive behaviours and so on. Nobody gets to play judge here. Shopping is like this. Buying and eating food. Buying a new vehicle. Our paycheque. A college degree. Going to heaven. You name it. When we feel turned on and motivated about and towards something, this very old system is very much at the root of it. (1)

About the only difference in humans is the variety of things we'll do in order to achieve that reward and the time we'll take to achieve it. Not to mention what we'll put up with to achieve it. We can stay locked on a dopamine anticipation loop for years. That's the "planning and judgment" parts of our vaunted frontal lobes that plays a role. 

Okay, so there's the "up side". 

Now to us depressed, demotivated peeps who struggle with feeling pleasure and sticking with things.

What's up there?

Now is the time to understand that we're somewhat more complex than mice (or primates or lizards or birds or ...) after all.

To understand "us", let's go back to the diagram. You can see that these all important motivation and pleasure pathways originate in a deep brain nodule called the Ventral Tegmental Area. 

Let's look at a more isolated image showing the VTA. 


That's where dopamine originates (a process the details of which we'll leave to more advanced brain nerdery). 

We can think of the VTA as a "switchboard" lady like we saw in the image above. 

Now, what's extremely unfortunate in virtually all the images we see depicting the dopamine pathways (and serotonin, for that matter ... or any region of the brain) is that they do not show the massively complicated feedback loops connected to the VTA, the incoming circuitry. The VTA switchboard lady doesn't just sit there all by herself ringing up our frontal lobes and whatnot getting us all excited and motivated all on her own volition. No, no, no. That's more akin to lizard level dopamine pathways. Our "human grade" VTA Lady has dozens and dozens of incoming circuitry sending information packets or demands of varying sorts. She takes an incoming call - "shoe sale ahead!", for example - and connects that to the pleasure/reward destinations in the brain. 

These "calls" can come from all over the brain. Which, despite our remarkable similarities to lizards, baboons, birds, dogs and all other animal species, is what makes humans vastly more complicated and varied; for all the circuitry that can potentially stimulate the VTM is an incredibly complex set of feedback networks (yes, yes, I know what many of you are thinking but really, we are more complicated, even the persons you may regard as simpletons). 

It's these incoming calls that we want to better understand. What rings up VTA Lady? What rings her bell? Or, to understand lack of motivation and pleasure, what does not ring her bell?

Okay, mentally suffering peeps, this is where the rubber meets the road in our understanding of our moods and this deep brain system involved with them. 

Let's look at one such feedback loop system, one that may be the most important - and the most uniquely human.

I talk in numerous posts a lot about belief. Various brain circuits involved in creating and disseminating back to us our beliefs are a huge feedback loop to the Ventral Tegmental Area (hereafter known as "VTA Lady"). Belief and imagination are tightly linked and it is the belief of good things to come and the strong imagination thereof that will often keep us moving forward despite possibly great odds against us or obstacles in our way. This can be seen throughout our evolutionary history (and is thus tightly linked to religious beliefs and the comforting and motivating thoughts of going to heaven). A lot of what we think is "good behaviour", for example, is really just having a really strong connection to VTA Lady keeping that pleasure/reward system locked on to a goal related to beliefs associated with religious morals (sorry, morally superior feeling people).


So, let's look at this through the lens of our experience. 

We don't get "depressed" and demotivated out of the blue for no reason (though I know it feels that way; this is the big disconnect between our subconscious brain mechanisms - like this one - and our conscious awareness or experience that I often refer to). 

If you look back on your life, all kinds of painful events will have pounded the living shit out of your beliefs and motivations. So often your greatest beliefs and desires have been crushed by life. We often keep going, but for a variety of possible reasons, we get crushed again and again. This will begin to have effects on all the circuitry involved in motivation and pleasure we're looking at here today. The feedback system just keeps sending too many painful messages to VTA Lady. Pain becomes too associated with desired rewards. VTA Lady just gets to the point where she says "fuck this shit, I'm not taking any more calls from that belief area". And after a while, the lines of communication between various brain areas associated with beliefs and VTA Lady begin to atrophy (literally). Worse yet, because of the resultant lack of stimulation the areas in the brain associated with feeling the hits of dopamine and thus pleasure and motivation begin to atrophy as well. This is part of what some think of as the "dark side" of neuroplasticity

And this same process can happen with many of our goals and desires as we experience defeat, disappointment, hurt and other negative impacts and results for things we started out feeling excited and motivated about.

There are people who are more resilient to this, but for many of us for a number of reasons this is a huge part of the process that creates the sense of "giving up" that we so strongly experience so often as part of depression. 

So there's that. 

But we may also notice other painful experiences associated with what we'd normally think of as motivating and pleasurable and this too will send negative feedback information to VTA Lady and again, after a while she just throws in the towel and stops taking calls from those areas. And slowly, bit by bit, almost without being aware of it, we find ourselves getting more and more down and demotivated and less and less able to feel pleasure, excitement, senses of gratification (a kind of reward feeling) and/or be unable to feel any "good" sense of anticipation. There will probably have been major blows and a good number of smaller ones. Either way, gradually our abilities to feel motivated and pleasure are eroded. This is not our imaginations, this is the result of actual changes in vital brain circuitry; the circuitry outlined here in the dopamine motivation/reward system. 

However, in a good number of people where pain and pleasure get "crosswired" in key areas of the brain they actually become motivated to seek pain and their dopamine pathways become somewhat tragically dialed into these behaviours. Something to consider when we try to understand seemingly incomprehensible behaviours like cutting, carving or why people keep returning to abusive relationships and other what appear to be destructive behaviours. This is a very dark side to neuroplasticity indeed (I may at some point get to recounting some very interesting case studies and the inspiring resolution of them).  

Or - OR! - this system may get "hijacked" and drive us towards behaviours that seemingly dull our pain by giving us pleasure elsewhere. Hello almost all addictive behaviours. There is some very good recent clinical and real world research (2) that is now more deeply understanding the very strong relations between pain and trauma, the dopamine reward system and destructive/addictive behaviours of all kinds. Very important to understand and keep in mind. 

Okay, now that we have a better understanding of all that - or at least the seed of understanding planted - we come to the $64,000 question. What the hell to do about it?

Regular readers should see the first two coming - we begin with self-forgiveness and compassion for ourselves. For if you are struggling in any of the ways we looked at here, that is not "you", but instead very deep and powerful brain systems that for all kinds of very strong reasons have gone awry. "You" don't just reach in there and magically fix that. Nor does "helpful" advise from well meaning friends and relatives. This is why you can't just "cheer up" on demand. Deep stuff is not as it should be. 

So can we get it back to, or at least closer to, what it "should be"? 

Yes.

This is what many people have successfully done and continue on the road to doing. This is why I talk about the importance of belief, thoughts, spirituality, brain training, the concept and power of neuroplasticity and so on. For it is small daily tasks that will slowly dampen down the pain circuits and rebuild better hope and belief circuits that will begin to reawaken motivation and pleasure regions involved. This is why I work on at least some or even just one or two, of my positive difference making fundamentals daily - all of those can help to repair and rebuild what we briefly looked at here today. 

In other words, what we need to do, in essence, is rebuild the dormant or broken down communication lines to VTA Lady who will in turn start to "ring up" and connect us to the feelings of more proper motivation and pleasure that we so often struggle with and away from those "rewards" we've been driven to seek to dampen pain. 

We will look more deeply at how meditation and mindfulness CBT can help, how certain positive visualization exercises can help, how specific mental and physical "letting go" exercises can help and much more. 

And I know - I deeply know - that it is not easy. But I can assure you one hundred percent through my experience, that of dozens of case studies and just by the pure science of how it all works that is possible. Even for you. Yes, you.

What's important to know and understand, however, is that we can never go back to who we were and what we had before. This is why the practice of letting go is so important. We must learn bit by bit let go of past events and models of ourselves in order to set our aims to new horizons, to slowly build new and pleasurable memories and thus a changed person. Again, I deeply know how hard that is.

But step by step, day by day, if we take the right steps, we can get there. 

Yes. We. Can. 

Thank you as always for reading. 

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(1) Contrary to the belief of some (or many, who knows), I do not randomly make this up. I have very solid and world renowned go-to sources for everything I write, and I am merely taking their findings and reporting it to you, the reader, often in very similar ways to how they explain their experiments and findings. 

(2) In a future more academic version of the posts of this blog, I will include many more source citations for segments like this. 

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