I'm hopeful someone more educated than I can explain this paper in layman's terms so I can ponder, digest, and research what it says.

From what I can tell, it discusses the role that norepinephrine plays in executive functions.

http://www.behavioralandbrainfunctions.com/content/pdf/1744-9081-4-12.pdf

Help?? :confused:

Even neuroscientists can't explain the Frontal Cortex. Or the PFC or the OFC (my personal favorite).

It's got so many subparts and sub-sub-parts and so much going on, let alone the chemistry of it! Not only do regions control actions, but they also control INHIBITIONS. (e.g. the brakes)

The paper you are looking at is basically a Lit Review. That means it is an author looking at other researcher's work and distilling down the gist of what THEIR paper's said. (Notice how there are 84 references! Almost 1/2 the paper is other researcher's papers.)

Yes it talks about things like spatial WM (working memory) which is a KEY Executive Fx.

e.g. "Spatial WM" says to me that they are using Rats as models for their memory research.

What are you more specifically wanting to know?

--

P.S. They give the Crux of their conclusion in the "Conclusions" section. (Alternately research papers will call it a "Discussion" section.)

DD has always been on stimulants (mph first, then adderall, now vyvanse), but we really haven't tried very much else; brief trial of Strattera, but at the time she was on too high a dose of Daytrana, which confounded everything. I'm trying to figure out if this is saying, "Hmmm. It appears that problems with executive function may be better addressed by noradrenagenics." I've always assumed we were trying to address an under supply of dopamine. Should we be trying to stimulate norepinephrine too/instead if the primary symptoms are working memory, judgment, organization, etc. rather than hyperactivity?

DD has always been on stimulants (mph first, then adderall, now vyvanse), but we really haven't tried very much else; brief trial of Strattera, but at the time she was on too high a dose of Daytrana, which confounded everything. I'm trying to figure out if this is saying, "Hmmm. It appears that problems with executive function may be better addressed by noradrenagenics." I've always assumed we were trying to address an under supply of dopamine. Should we be trying to stimulate norepinephrine too/instead if the primary symptoms are working memory, judgment, organization, etc. rather than hyperactivity?

I have heard before that noradrenergics are more effective in people without hyperactivity (I think it was girls?).

But certainly, norepinephrine is a vital part of ADHD medicine.

Note that while noradrenaline may be PNS active like adrenaline, unlike adrenaline, and like dopamine, it is also CNS active.

Upon reading the abstract, it appears to be saying that both dopamine and norepinephrine together produce a holistic treatment of ADHD (stimulants), but that norepinephrine on its own can show improvements and be useful if other stimulants don't work. Dopaminergic only agents don't seem to be effective.

Interestingly, Guanfacine appears to be an noradrenergic inhibitor drug used for ADHD. While Atmoxetine is a noradrenergic activator drug used for ADHD. How does that work?

I'm hopeful someone more educated than I can explain this paper in layman's terms so I can ponder, digest, and research what it says.

From what I can tell, it discusses the role that norepinephrine plays in executive functions.

http://www.behavioralandbrainfunctions.com/content/pdf/1744-9081-4-12.pdf

Help?? :confused:
Just to confuse things a bit more (grins):

There is no ‘executive function’ in the human brain or mind.

The behavioral model of brain function of which ‘executive function’ is but one small part was developed as a framework for discussing behavior.

It was never intended to be taken as literally implying the existence of a functional equivalent physical area of the brain, such as the prefrontal cortex.

There is no doubt the prefrontal cortex exists, of course, but its function is not as commonly assumed by AD/HD researchers.

The originators of the descriptive models that include ‘executive function’ were clear that we shouldn’t expect to find that real neural mechanisms work anything like the model, and at least two independent paths in our own work verify their suspicions.

When we look at how neurons function to provide models of behavior, there isn’t any need for an ‘executive’ mechanism. The appearance that some ‘executive’ is at work is predicted, but the illusion arises as a consequence of the odd, somewhat counterintuitive way that neural structures work.

(At the highest levels, the persistent impression that an ‘executive’ must exist is also predicted. The mind can be a funny thing, eh?)

You might want to skim through the thread Thoughts on ADD and the prefrontal cortex in this same sub-forum for a more complete discussion of the scan data that is widely misinterpreted to support these ideas about the role of the prefrontal cortex.

And please feel free to ask any questions that you might have about this or our own work, either here or in a PM. We have no doubts about the efficacy of drugs that have been shown to have value in treating AD/HD in clinical studies, but the current weak attempts to interpret the effects on the neural level are way off the mark.

It’s not a surprise you’d find them confusing. Fortunately, you don’t need to understand the underlying mechanisms to get an effective result in treating AD/HD; in our experience, knowing details about what’s going on at the neural level doesn’t have much practical value.

It’s understanding the effects on a people level that seems to help the most.

--Tom and Kay

Interestingly, Guanfacine appears to be an noradrenergic inhibitor drug used for ADHD. While Atmoxetine is a noradrenergic activator drug used for ADHD. How does that work?That's a complex question. The noradrenaline containing neurons have a number of ways that they regulate noradrenaline release.

There are multiple ways drugs can act on the noradrenergic system. Atomoxetine is a reuptake inhibitor, meaning it increases the amount of noradrenaline that is available to stimulate noradrenergic receptors, by preventing it from being sucked back into the neuron from which it came.

Guanfacine stimulates a subtype of noradrenergic receptor which is located not only in the prefrontal cortex on neurons which aren't noradrenergic, but also on the noradrenaline neurons themselves.

Stimulation of the receptors on the noradrenergic neurons themselves invokes a negative feedback loop, which eventually shuts them down. But, guanfacine is also stimulating the prefrontal cortical neurons as well, so it's not entirely inhibitory. Incidently, the rise in noradrenaline concentration caused by Atomoxetine would probably also eventually shut down the noradrenaline neurons themselves, so the net effect of the two drugs could actually be quite similar.

This is actually a question I addressed a bit in my thesis; it's actually a really good research question, because IMHO, nobody really has a good explanation of which of these functions actually is therapeutic in ADHD.