• Welcome to Phoenix Rising!

    Created in 2008, Phoenix Rising is the largest and oldest forum dedicated to furthering the understanding of and finding treatments for complex chronic illnesses such as chronic fatigue syndrome (ME/CFS), fibromyalgia (FM), long COVID, postural orthostatic tachycardia syndrome (POTS), mast cell activation syndrome (MCAS), and allied diseases.

    To become a member, simply click the Register button at the top right.

Motivation (cognitive symptom)

xena

Senior Member
Messages
241
I'm trying to figure out how to address my pretty low motivation. Tldr: what parts of the brain or neurotransmitters are involved in generating motivation? Working memory? Any suggestions (chemicals, psychological interviewing) for addressing that?

@Hip @aaron_c?

I could probably accomplish more cognitively and physically than I do. I almost never have PEM from every day activity anymore but basically spend all day in bed from the feeling of significant fatigue. On the rare occasion that something works decrease my brain fog significantly, I feel much more motivated to do stuff. The way things are, I have a reasonable amount of cognitive energy and my focus isn't even too bad. But I don't have the motivation to do much other than medical googling and intimate relationship...

I've noticed that things that seem to affect the hypothalamus make a particular difference... Like hypothalamus glandular, cold showers or vitamin a
 

Hip

Senior Member
Messages
17,824
@xena
In this post I detail two treatments that I found helped my low motivation symptoms: low dose pramipexole, and vitamin B2.

In this post on the HR forum I describe my own quite severe low motivation symptoms that plagued me a few years ago. I will copy that post below for reference:
At my worse stage of ME/CFS, around 6 years ago, I did have really significant and pathological problems with low motivation.

For example, if I'd spilt some coffee on my desk, the normal healthy response would be to get a cloth or some tissues to clean it up. This response would be so automatic, you would not even consider it as an issue. But I'd often find myself just numbly staring at the situation, but somehow my brain would not engage in the simple task at hand (to clean up the desk in this example).

This was not because of fatigue, nor because of brain fog making the task too difficult to do; no, it was genuinely something amiss in the motivational circuitry of my brain. You clearly saw and understood what needed to be done, but the brain would not engage in the task. It was if there was something jamming the brain. It sounds weird, but that's how it was.

This same low motivation occurred in hundreds of very small and easy to do tasks. You knew what had to be done, you knew how to do it, and it was fairly easy and straightforward to do, but somehow the brain would not initiate and engage in the activity. It's hard to imagine this if you have not experienced it, but such pathologically low motivation can be a pretty significant condition.

It seems that the motivational circuits of the brain actually help coordinate and initiate the brain into purposefully tackling the task at hand; but without this coordinating prompt from the motivational circuits, the brain just sits there and does nothing, in a sort of numb state (even if the brain is very aware that the task needs to be attended to).

I became quite aware that I had low motivation, and realized it was a problem, but did not have a solution for it. You would not call my condition laziness, because I genuinely did not want to be like this, I wanted to find an answer to this problem, but for some years I couldn't figure out a solution.

However, by chance I discovered that low doses of pramipexole (half of a 0.18 mg tablet) worked wonders for boosting my motivation, and I found that when taking pramipexole, I'd spontaneously start doing things that needed to be done.

At the time, pramipexole was a really effective solution for me, because as anyone with ME/CFS knows, there always seems to be so much to do as an ME/CFS patient (new reports to read, new drugs or supplements to order online and then try out, emails to answer, topics to study, etc).

I was really in a hole with my ME/CFS at that time anyway, because my ME/CFS was becoming worse (moving towards severe), and I really wanted to try to find some treatment solutions that could hopefully halt the decline. But the low motivation just seems to numb and jam my brain, preventing me from engaging in purposeful activity. So in that period of my illness, pramipexole worked well, and helped me become more purposeful in my tackling of ME/CFS. I also found vitamin B2 helped with motivation.



Lack of motivation is slightly different to anhedonia (which I also suffered from). Lack of motivation means you do not tend to initiate into tasks and purposeful activity; anhedonia simply means that you don’t get the feeling of reward or satisfaction on completion of a task. Lack of motivation is due to problems in the motivational circuitry of the brain; anhedonia is due to problems in the reward system of the brain.

I should note though that my ME/CFS began shortly after viral meningitis, that quite significantly affected my brain, so this may be why I suffered from these problems of crippling low motivation and severe anhedonia. Generally, neither low motivation nor anhedonia are considered part of ME/CFS, though I guess some ME/CFS patients may experience these symptoms.


These days my motivation is reasonable; I get a reasonable amount done each day (within the limits of my brain fog and mental fatigue).

More recently, when I was experimenting with some Russian Staphylococcus alpha toxoid vaccine injections which I was hoping would improve my ME/CFS symptoms (so far they have not), I noticed that in the week or two after injecting the vaccine, I became much more motivated. Ideas or projects that I had in the back of my mind for years I would suddenly find myself engaging in. So somehow this vaccine was boosting motivation (and it also boosted my mood). The vaccine did not help with the brain fog or fatigue of ME/CFS, though.
 
Last edited:

Hip

Senior Member
Messages
17,824
In this post on the same HR forum thread details some areas in the brain that are involved in motivation:
I should add that pramipexole worked well for me during that more severe period of my ME/CFS, boosting motivation and also boosting mood; but as my ME/CFS improved (likely as a result of my high dose selenium protocol I think), the dynamic in my brain seemed to change, and the very same dose of pramipexole started to have negative effects: it started to cause emotional weakening and frailty, created a feeling of mental unease, it reduced my desire to socialize with people, and its motivation and mood boosting effects disappeared.

So pramipexole worked well for me at the time when my motivation was pathologically low, but later as my health improved, it no longer worked, and started to have negative effects.

But this drug has been shown to improve motivation in Parkinson's disease, so clearly it has a motivation-boosting potential.


Both motivation and reward are linked to dopamine, though it's hard to find any clearcut rules of thumb about which dopamine receptors you need to target for increase motivation, though the dopamine D2 receptors in the nucleus accumbens come up. Here are some studies:

Here is a list of dopaminergic drugs and supplements.



I think you hit the nail on the head with that phrase: "natural motivation". Motivation is a definitely natural and automatically-acting feature of the brain. You don't notice that you have this wonderful motivational circuitry in your brain until it goes wrong, and then you notice it by its absence. But when it is working, motivational responses to situations do occur naturally, spontaneously and moreover effortlessly.

In healthy people, we see differences in motivational levels, but I think this just comes down to genetic differences in the motivational circuitry of the brain. Highly motivated people sometimes present themselves as being people to look up to, because of their motivational drive, but it probably just comes down to the well-functioning motivational circuitry they were blessed with. My view is that motivation is a natural and automatic response that is actually effortless when it works properly.

In fact, this article and study expresses this nicely: Brain structure may be root of apathy. In this MRI study, that found that more apathetic, less motivated people actually made more effort in their brains when tackling tasks!

And this reflects my own experiences of pathologically low motivation, where it did require an enormous amount mental effort on my part to try to force my brain to engage in tasks that needed to be done. But now my motivational circuitry seems to be working a bit better, I more easily and spontaneously engage in tasks, without needing to exert much mental effort.

So in normal life, people with high motivation likely expend very little mental effort when initiating into a task, whereas for people whose brains are more apathetic, it takes a great deal of mental effort to engage in purposeful activity.

That finding sort of turns everything on its head: it may be the apathetic who are mentally making the most effort in life!


And from this post on the HR thread:
the striatum, which is located in the basal ganglia, is "a center of reward and motivational signaling in the brain."

a couple of studies that indicate pramipexole can ramp up dopamine in the striatum. So that might well explain why I found pramipexole boosted motivation.
 

junkcrap50

Senior Member
Messages
1,330
Hip does a great job in his posts. But in short: lack of motivation = low dopamine. And how to increase dopamine is like the holy grail.

I would be very careful with pramipexole aka mirapex. I had a family member on it for restless legs and it made him/her extremely impulsive and have a shopping/spending addiction. Impulsiveness and addictive behavior are known side effects. ADD/ADHD medications like adderall seem to work much better, have fewer side effects, and be safer. I woud try those drugs first and other noortropics before any hardcore drugs for parkinsons.
 

Alvin2

The good news is patients don't die the bad news..
Messages
2,995
Fixing motivation with drugs is a bad idea, not only are you likely to have adjunct problems but your falling into the biochemical trap, all behaviours are a matter of biochemistry instead of being human emotions. This is seen in the zeal to treat psychological problems with drugs, for example depression is a loss of hope, drugs don't fix this problem, they artificially throw brain chemistry out of whack and when you feel energized by this its called a successful treatment. No different then using alcohol as a crutch, except you should not be inebriated by anti depressants. Yet we realize alcohol addiction is a bad thing, but "happiness" drugs are medical hence good. Oh and many antidepressants are addictive.


Hip does a great job in his posts. But in short: lack of motivation = low dopamine. And how to increase dopamine is like the holy grail.

I would be very careful with pramipexole aka mirapex. I had a family member on it for restless legs and it made him/her extremely impulsive and have a shopping/spending addiction. Impulsiveness and addictive behavior are known side effects. ADD/ADHD medications like adderall seem to work much better, have fewer side effects, and be safer. I woud try those drugs first and other noortropics before any hardcore drugs for parkinsons.
I agree about avoiding mirapex, it has been found to cause compulsive gambling, sexual compulsions and other crazy behaviours. Best avoided even if you have Parkinsons until you have no other choice and even then proceed very carefully.
I don't agree with using ADHD drugs, again a toxic reaction is considered a treatment. Docileness is a good thing when students don't bother teachers and people want to quiet down their ambitions but again screwing with your mind is not a good thing.

With this condition we do have many negative cognitive effects but trying to fix them by throwing neuroleptic drugs at it is like trying to fix a leaky roof with dynamite. By throwing mind altering drugs at this you may end up with permanent brain damage because your screwing with the the biochemistry of your brain that we barely understand.
 
Last edited:

Basilico

Florida
Messages
948
I agree with the posts above. I have gone through periods of extremely low motivation and the only things that I found to consistently help are things that supported my neurotransmitters (which is ultimately at the heart of this problem).

Rather than taking a medicine that temporarily increases production of dopamine (which is temporarily awesome but will ultimately lead to a decrease in receptors, thus exacerbating the problem), I prefer to take something that prevents the dopamine I have from getting broken down too quickly.

I have had excellent results with Selegiline (brand name for L-Deprenyl), which is a MAO-B inhibitor. I used it for depression which unsurprisingly was coupled with an extreme lack of motivation. It slows down the premature breakdown of certain neurotransmitters (dopamine and phenethylamine).

Selegiline is also really interesting in that it protects against neurotoxicity, and many people take it as an anti-aging supplement; there is a lot of research on its neuroprotective abilities.

You don't need a prescription to order it online; I order it from a reputable online UK pharmacy. I've been meaning to pick up another bottle since I haven't taken it in a while. I would ideally like to be taking it on a regular basis, but I can only afford so many supplements at once! I tried one form that was in liquid form and worked really well, but the last time I tried a different brand that was in tablet form, and it didn't seem to work as well. If you are interested, I will look up the original one I took that worked well and the name of the pharmacy.


In case you are interested:

https://www.ncbi.nlm.nih.gov/pubmed/12872288

https://en.wikipedia.org/wiki/Monoamine_oxidase_inhibitor#Mode_of_action
 

caledonia

Senior Member
I found some info that says you may be able to increase dopamine by increasing vitamin D. I had increased mine a month or two ago to see if it would help leg twitching at night which continues despite being maxed out on magnesium and potassium.

I don't know if it's really helping that, but my motivation does seem to be somewhat better.

Or it could be that I'm actually sleeping a bit better and so have a bit more energy. Doesn't really feel like it to me though.

I found out I have a gene mutation that causes vit. D3 not to be as well absorbed. My D levels are always a borderline suboptimal despite supplementation. The gene is called GC. There doesn't appear to be an rs number for it. I'm +/-. This is from the PureGenomics report.
 

junkcrap50

Senior Member
Messages
1,330
I have had excellent results with Selegiline (brand name for L-Deprenyl), which is a MAO-B inhibitor. I used it for depression which unsurprisingly was coupled with an extreme lack of motivation. It slows down the premature breakdown of certain neurotransmitters (dopamine and phenethylamine).

Selegiline is also really interesting in that it protects against neurotoxicity, and many people take it as an anti-aging supplement; there is a lot of research on its neuroprotective abilities.

I also recommend Selegiline. I've taken it and it does work well for me.
 
Messages
3,263
Hi @xena, low motivation goes with the territory. Its all connected. Let me explain:

There's a part of the brain, the anterior cingulate, that becomes active when we want to "make an effort" on some mentally challenging task. What this structure does is "fire you up" to do the job by raising your blood pressure and inducing changes to your heart rate and other stuff, so that more blood flows into the bits of brain you need for the job. Then you're more able to summon those extra mental resources needed to do the difficult task.

If you are physically ill - especially if you're fatigued - its likely that your anterior cingulate won't be able to do its job of "firing you up" effectively to put mental effort into things. Not its fault, your body is not effective at doing the stuff that's required (blood pressure, heat rate changes etc.). So its really hard for MECFS people to summon the resources for really effortful thinking.

Now here's the motivation bit: thinking in a motivated way requires mental effort - you have to have a goal in mind, think of possible ways to achieve it, etc. etc. If you can't summon that effort, you can't do it effectively.

People often think of raised heart rates and things like that as to do with emotion. But what I'm talking about here is really different. Our body's response to fear, threat etc. is kind of involuntary and above all, easy. But this "effortful control" thing is voluntary and takes real physical effort. And we use it when we decide to, not just when we're feeling "emotional".

So you could easily have a lack of motivation but not be depressed. The fatigue is just crushing your ability to think ahead and get fired up mentally about things. Its also causing the brain fog too (that's pretty much the definiton of not being able to put in mental effort).

What to do about it? If you can fix the fatigue, you can probably fix the motivation (in fact, your already said that pretty much). So maybe think body, not head? If you don't get PEM, you could try some light exercise, just gently see how it goes? That might lift it a bit, if you can get away with it. I know some MECFS people have tried stimulants like ritalin and say they work. I'm a bit worried about that though. Can you drink coffee? (lots of us can't).

A cold bath might lift the fatigue for a few hours or even a day if you're lucky. Hard to do, though.

Make sure you drink lots and get lots of salt. Some of us have low BP and that will probably make it worse.
 

xena

Senior Member
Messages
241
Thank you very much everyone!

@Hip love the information you have put up

One thing I forgot to mention that magnesium l threonate helps me a LOT for a few hours.... Then it makes me horribly depressed
 

Hip

Senior Member
Messages
17,824
@xena You might like to look at the Wikipedia aboulia article. Aboulia is the name of one of the disorders of low motivation. The treatment section of that article says dopamine agonist drugs and cholinesterase inhibitors help. Galantamine is a cholinesterase inhibitor supplement.
 

Jigsaw

Senior Member
Messages
420
Location
UK
I found some info that says you may be able to increase dopamine by increasing vitamin D. I had increased mine a month or two ago to see if it would help leg twitching at night which continues despite being maxed out on magnesium and potassium.

I don't know if it's really helping that, but my motivation does seem to be somewhat better.

Or it could be that I'm actually sleeping a bit better and so have a bit more energy. Doesn't really feel like it to me though.

I found out I have a gene mutation that causes vit. D3 not to be as well absorbed. My D levels are always a borderline suboptimal despite supplementation. The gene is called GC. There doesn't appear to be an rs number for it. I'm +/-. This is from the PureGenomics report.
@caledonia

Re restless legs (if I've understood "leg twtiching at night" correctly).

I found that taking 3mg MB12 stopped it dead within 20 minutes.
 

Mary

Moderator Resource
Messages
17,334
Location
Southern California
I almost never have PEM from every day activity anymore but basically spend all day in bed from the feeling of significant fatigue. On the rare occasion that something works decrease my brain fog significantly, I feel much more motivated to do stuff. The way things are, I have a reasonable amount of cognitive energy and my focus isn't even too bad. But I don't have the motivation to do much other than medical googling and intimate relationship...

I agree with @Woolie that your significant fatigue is probably a huge factor in your lack of motivation. Who feels motivated when they are very tired? So I think it would be good if you focused on finding the cause of your fatigue, and this will I'm sure take a lot of work and experimentation.

Re dopamine: I've been reading that low dopamine is associated with diminished libido, so from what you say, it may not be the source of your fatigue and lack of motivation, although low dopamine is associated with fatigue. I know very little about dopamine but this jumped out at me after a very brief search.

These things have all caused fatigue for me: low potassium, low B1, low B6, low folate, low B12, low phosphorous, low cortisol, low thyroid, weak adrenals, low stomach acid (prevented absorption of nutrients), high levels of toxins in my liver - and this is all separate from PEM. Some of this I found through trial and error, and some of this was discovered through Nutreval testing. But if I had not addressed each of these issues, my energy would be worse than it is now. Also, a chiropractor who does muscle testing helped me with some of these issues.

Also - what drugs (if any) are you taking? Fatigue is a very common "side" (actual) effect of many drugs.

What supplements do you take, and what doses?

It's interesting to me that magnesium threonate seems to help you so much but then leaves you depressed. It's a puzzle to me. I haven't heard of magnesium depleting any particular nutrient, though it's a possibility. Have you tried other forms of magnesium? Maybe you would tolerate a different form better. Low magnesium can cause fatigue too. You may have normal magnesium levels on standard blood work but it can be low intracellularly. There's a magnesium RBC test which measures magnesium inside the cells which might be a good thing for you to do.

It's great you don't have PEM. I think it's very possible that you may just have some nutritional deficiencies which in my experience are much easier to treat than PEM.

Are you working with any type of doctor or health practitioner on your fatigue? I have found that generally integrative or functional medicine doctors and naturopaths are best for this type of issue because they know more about health and nutrition than regular MDs. Regular MDs seem to just focus on handing out drugs to combat symptoms without getting to the root of anything. Or else they'll tell you're depressed because your blood work is normal.
 

Jigsaw

Senior Member
Messages
420
Location
UK
Yeah, unfortunately I can't take any more than 20mcg of MB12 per day or I crash.
I crashed very badly when I switched from taking MB12 Dr's Best 1.5mg capsules for my restless legs, to MB12 1200mcg patches, every other day. It's what brought me here. I applied various methylation protocols, and I stayed crashed. I was fantastic for a few energy-filled weeks, then hit a wall. Horrible. I had to stop it completely, and I've stayed stopped. Now concentrating on iodine supplementation instead.

I tried MB12 injections, following a severe reaction to a single 1mg HB12 injection. No toxic reaction to MB12 injections, but still no energy and stayed crashed. Tried with all the relevant co-factors, nothing doing :-(

I seem to tolerate sublinguals and capsules occasionally, but something goes wrong if I use MB12 on a regular basis, so I can relate to your problem with B12. (I also don't convert B2, I have to take FMN. Riboflavin makes me feel violently sick. Every time.

What happens to you when you take more than your limit, in terms of crash symptoms?
 

caledonia

Senior Member
I crashed very badly when I switched from taking MB12 Dr's Best 1.5mg capsules for my restless legs, to MB12 1200mcg patches, every other day. It's what brought me here. I applied various methylation protocols, and I stayed crashed. I was fantastic for a few energy-filled weeks, then hit a wall. Horrible. I had to stop it completely, and I've stayed stopped. Now concentrating on iodine supplementation instead.

I tried MB12 injections, following a severe reaction to a single 1mg HB12 injection. No toxic reaction to MB12 injections, but still no energy and stayed crashed. Tried with all the relevant co-factors, nothing doing :-(

I seem to tolerate sublinguals and capsules occasionally, but something goes wrong if I use MB12 on a regular basis, so I can relate to your problem with B12. (I also don't convert B2, I have to take FMN. Riboflavin makes me feel violently sick. Every time.

What happens to you when you take more than your limit, in terms of crash symptoms?

It feels like post exertional malaise - flu like muscle and joint aches, extra fatigued.

Same deal with too much folate. Feel good at first, then a crash. These days, I get my folate from leafy greens. 3 leaves is my limit. o_O
 

Prefect

Senior Member
Messages
307
Location
Canada
In this post I detail two treatments that I found helped my low motivation symptoms: low dose pramipexole, and vitamin B2.

I have had excellent results with Selegiline (brand name for L-Deprenyl), which is a MAO-B inhibitor. I used it for depression which unsurprisingly was coupled with an extreme lack of motivation. It slows down the premature breakdown of certain neurotransmitters (dopamine and phenethylamine).

I also recommend Selegiline. I've taken it and it does work well for me.

Folx I've mentioned before my entire illness of 20 years has been cognitive, dizziness, neurological stuff many CFS patients have, but my body is fine, I exercise 3 times a week with no change in my symptoms (and I don't get better or worse if I stop for a few weeks). But this condition did start with an accute systemic illness that had gastrointestinal symptoms.

I've noticed when I partake in activities that are distracting but in a very emotional way many of my symptoms resolve. Especially when I suspect these activities produce dopamine. When I get time to write songs (I'm a musician) for instance, during the entire period I'm practically symptom free, to the extent that when I finish after a few hours I get the same sense of anxiety take over that I get when I wake up in the morning. Or when I get very emotional and cry, the sides of my head tingle and I become symptom free for an hour or so.

So I either have severe conversion/disassociative disorder from PTSD (which I doubt I have, this illness is the most traumatic thing that's ever happened to me) that I snap out of during strong emotion, or dopamine release has a therapeutic effect on my head. I should mention the week I got sick, I was so ill I quit smoking. I was a VERY heavy smoker up to then. Nicotine is dopaminergic.

I would like to experiment with ideas for increasing dopamine without what you folx call "crashing". I've taken 500mg tyrosine twince on an empty stomach before with no impact.

I would welcome any ideas. I'm currently going off my SSRI of 20 years (Luvox) and am willing to give an MAO Inhibitor a try if I don't have to stop eating fermented food, cheese, dark chocolate. And wine. I can't go without my glass of wine at night.

Any help would be appreciated.
 

Basilico

Florida
Messages
948
@Prefect , how to raise dopamine without crashing afterward, this is the million dollar question! As far as I know, probably the best way to go about doing this with a MAO inhibitor - as I mentioned before, I've had good results with Selegiline. I just learned of a newer medicine available which I am about to order for myself because I think it has potential to work even better than Selegiline. It's Moclobemide, and the great thing about it is that it's a REVERSIBLE MAO inhibitor, so there is no need to be super vigilant about food restrictions. I would strongly recommend looking into this to see if it could help. It's currently not approved for use in USA (for no good reason), but is approved in many other countries like Australia and UK, and is available to buy from online pharmacies. I'm not sure what the status is in Canada.

Here is a link, in case you want to read about it: https://en.wikipedia.org/wiki/Moclobemide

My husband and I both experience to some degree what you described - during brief windows of time, when we are actively engaged in something we love, we temporarily feel a huge improvement. There is clearly some signal that is able to override the "sick behavior signal" in our brains.
 

Prefect

Senior Member
Messages
307
Location
Canada
My husband and I both experience to some degree what you described - during brief windows of time, when we are actively engaged in something we love, we temporarily feel a huge improvement. There is clearly some signal that is able to override the "sick behavior signal" in our brains.

I often suspect if the pathologic process acting in CFS messes up the CNS so badly that it creates a disassociative conversion disorder type state which presents with all the symptoms involved. Almost as if the disease process creates a similar state of mind and brain pathology that PTSD patients have, without actual traumatic events.

Maybe the shrinks are semi right. It really is all in our heads but in a really different way than they think. Jay Goldstein always thought so.

I live in Canada, it seems Moclobemide is available. I have an appointment with a psych doc in a couple of weeks, maybe we'll discuss this as an option.

I also have an appointment with a Naturopath (which I seriously dislike now, because she won't give me my GDX stool analysis results until I see her) in a couple of weeks, at which point I may also look into Mutaflor which you suggested before, depending on that the results say.