View Full Version : Norepinephrine and “High” Motivational Salience


ana futura
03-02-13, 06:45 PM
Can one of you sciencey types translate this for me?

http://www.plosone.org/article/info:doi/10.1371/journal.pone.0003044

Intense motivational salience attribution is considered to have a major role in the development of different psychopathologies. Numerous brain areas are involved in “normal” motivational salience attribution processes; however, it is not clear whether common or different neural mechanisms also underlie intense motivational salience attribution. To elucidate this a brain area and a neural system had to be envisaged that were involved only in motivational salience attribution to highly salient stimuli. Using intracerebral microdialysis, we found that natural stimuli induced an increase in norepinephrine release in the medial prefrontal cortex of mice proportional to their salience, and that selective prefrontal norepinephrine depletion abolished the increase of norepinephrine release in the medial prefrontal cortex induced by exposure to appetitive (palatable food) or aversive (light) stimuli independently of salience. However, selective norepinephrine depletion in the medial prefrontal cortex impaired the place conditioning induced exclusively by highly salient stimuli, thus indicating that prefrontal noradrenergic transmission determines approach or avoidance responses to both reward- and aversion-related natural stimuli only when the salience of the unconditioned natural stimulus is high enough to induce sustained norepinephrine outflow. This affirms that prefrontal noradrenergic transmission determines motivational salience attribution selectively when intense motivational salience is processed, as in conditions that characterize psychopathological outcomes.

Abi
03-02-13, 07:25 PM
Medications that provide norepinephrine, like Dexedrine, Adderall and Wellbutrin are good for ADHDers :p

ana futura
03-02-13, 07:36 PM
thanks professor Abi :rolleyes:

What I want to know specifically, is what is "high motivational salience"? And how specifically does norepinephrine affect it?

I have my own theories about motivation and Norepinephrine-

That norepinephrine is better for developing "long term" motivation (I should do my work, because if I do I'll feel good afterwards, and one day I might even get a career out of this),

and dopamine is better for "short term motivation" (I should do this because dopamine makes it interesting to me right now)

I want to know if this research supports my theory?

VOltaire
03-02-13, 09:21 PM
There called CNS stimulants for a reason.

SB_UK
03-03-13, 05:50 AM
... ... that selective prefrontal norepinephrine depletion abolished the increase of norepinephrine release in the medial prefrontal cortex induced by exposure to appetitive (palatable food) or aversive (light) stimuli independently of salience.

... indicating that prefrontal noradrenergic transmission determines approach or avoidance responses to both reward- and aversion-related natural stimuli Thanks - interesting.

The endocrine system and these super precursors like PMC (strange in the human genome) of 1 transcript which proteolytically cleaves into lots of different endocrine agents.

http://www.ncbi.nlm.nih.gov/pubmed/19587287Role of calcitonin gene-related peptide in light-aversive behavior

http://en.wikipedia.org/wiki/Calcitonin
Secretion of calcitonin is stimulated by:
an increase in serum [Ca2+]

http://en.wikipedia.org/wiki/Calcitonin_receptor [http://en.wikipedia.org/wiki/Amylin]
http://en.wikipedia.org/wiki/CALCRL

Connecting light, food (raising blood glucose), adrenaline, adrenal function (adrenomedullin), calcium and the pancreatic islet (glucose homeostasis).

I find that light (UV from February to October) suppresses food intake.

-*-

So - what's the connection between all of the above ? [see split thread in meditation and spirituality sub-forum (http://www.addforums.com/forums/showthread.php?t=141303)]

-*-

Adrenaline resistance (adrenaline sensitivity exposed to chronic adrenaline production) eg as seen in asthma (where b2 agonism is required to restore function - bronchodilation)
or
- the same basic effect (stimulant administration) is required to help the (stressed) ADDer out throughout educational system (stimulant sensitivity exposed to chronic stimulant (SNS activity) resulting in endogenous stimulant (norepinephrine neurotransmitter) resistance
- requiring exogenous stimulant administration to support functioning).

-*-

We require balance of the aversive/reward system - gradual diminuition until it 'dies' out ... ... where the ADDer - through hosting a stress response pushes the balance in the opposite direction.

SB_UK
03-03-13, 06:16 AM
So ... ... the overwhelming overlap between stress and stimulation - leads to the stress sensitive ADDer becoming resistant to stress-related hormones/neurotransmitters - requiring larger levels to excite us.
And all of this to a backdrop of the need to go in the opposite direction ... ... as we're (ADDers) scaling up the stimulation required (to resistance syndrome) - the mind (if it's building - which it's very hard to do as one reactively seeks stimulation) - seeks to take us in the opposite direction - to transcend the entire reward/aversion paradigm [also reactively].

Developing both resistance (through chronic stress exposure) and sensitivity (development of mind) simultaneously.

We're perhaps required to identify whether we're eating the wrong dliet.

Fast catch-up growth in Syndrome X'ers (which never stops leading to diabesity) is a sign that we are.

However - there is only one solution to this problem.

The Syndrome X'er/ADDer are reacting exactly as one would expect under stress - reaching for stress-relief ... ... leading to resistance syndromes in stress hormones/the stimulant system

... ... ... the sole solution to the emerging problem is to eliminate the stress which people feel ... ... by offering all people on the planet a zero energy home and sufficient food as a birth--right - by people doing for themselves.

We'd thereby decouple the need for money from survival - resulting in the only key stress which people are subject to - which is unmanageable.

SB_UK
03-03-13, 06:26 AM
So - it's true that we can connect eg endocrine imbalance (stress hormone resistance syndromes) leading to SNS/PNS imbalance leading to Insulin/IGF-1 (growth mode engaged) hyperactivity to the problems we face ... ... ... improper mental development, immune system and neurological system hyperactivity, societal collapse ... ... ...however there's no way of solving these problems without complete global re-definition of societal infrastructure - decoupling the need for money from happy survival.

We have all the science and technology we require to make it happen.

And so what're we waiting for ???

key point - convergence between stimulation and stress hormonal and neurotransmission systems - elevated hormonal / neurot. production - in stress/stimulant sensitive cohort resulting through negative feedback in resistance syndromes which have us reaching for stimulation in a bottle in order to engage/motivate.

Thing is - is that we're being stressed out attempting to engage in pointless (go nowhere) endeavours ... ... and so it's unsurprising that we react in this way.

AD(H)D - stress* sensitivity in an unnecessarily stress-ful world

The goal in life is to become a happy mitochondrial vessel - all that the mitochondrion wants is a bit of fat and oxygen - and an outer vessel which has some nice usage (aerobic exercise for instance) for its ATP
... ... driving mitochondrial biogenesis and more of the little chaps into action.

Our physical body (and to a large extent our mind) is all about the little guys.

https://encrypted-tbn2.gstatic.com/images?q=tbn:ANd9GcQAZEa5OLmWmxuzu3O00hpyRr2XIktaN OaPnkQARkZs3x9ZRaKthttps://encrypted-tbn3.gstatic.com/images?q=tbn:ANd9GcR2x1AR5C9sQ0_7A-mNR2_myGj8yEQYucuvA-ZhdLjmOTVpFZfBeA

Amtram
03-03-13, 11:09 AM
Intense motivational salience attribution
Salient: prominent, conspicuous, or striking. So this phrase refers to the amount of importance an individual places upon something that motivates him. In this case, it means cases in which the individual is motivated to a degree that exceeds what would be considered normal by something that may or may not be considered motivational within the general population.

is considered to have a major role in the development of different psychopathologies.
Meaning that this abnormal level of motivation by stimuli that might not be relevant to most people is a probable driving force behind the development of a mental illness.

Numerous brain areas are involved in “normal” motivational salience attribution processes; however, it is not clear whether common or different neural mechanisms also underlie intense motivational salience attribution.
Lots of different parts of the brain are involved in the reward system, so we don't know if these abnormal forms of motivation originate from normal reward systems working improperly, or if they originate from some different reward or reward processing system that's unique to the brains of these individuals.

To elucidate this a brain area and a neural system had to be envisaged that were involved only in motivational salience attribution to highly salient stimuli.
In order to figure this out, we had to create a brain model that responded only to the most influential reward-creating stimuli.

Using intracerebral microdialysis, we found that natural stimuli induced an increase in norepinephrine release in the medial prefrontal cortex of mice proportional to their salience, and that selective prefrontal norepinephrine depletion abolished the increase of norepinephrine release in the medial prefrontal cortex induced by exposure to appetitive (palatable food) or aversive (light) stimuli independently of salience.
In mice, using brain dialysis to measure changes in the blood concentrations of norepinephrine, we found that natural stimuli increased norepinephrine levels in the medial prefrontal cortex of their brains. The amount of norepinephrine was correlated to how "important," or rewarding, each stimulus was to the mice.

When the levels of norepinephrine were artificially decreased using the dialysis, that correlation went away. Even really tasty food and uncomfortably bright lights didn't change the norepinephrine levels anymore.

However, selective norepinephrine depletion in the medial prefrontal cortex impaired the place conditioning induced exclusively by highly salient stimuli, thus indicating that prefrontal noradrenergic transmission determines approach or avoidance responses to both reward- and aversion-related natural stimuli only when the salience of the unconditioned natural stimulus is high enough to induce sustained norepinephrine outflow.
However, this result applied only to highly rewarding stimuli, not the more normal, natural stimuli, so the importance of the stimuli (the intensely motivational salience) makes a difference in how much norepinephrine is produced above and beyond normal levels. Normal levels in response to normal stimuli is necessary to produce appropriate responses to stimuli based on their importance.

This affirms that prefrontal noradrenergic transmission determines motivational salience attribution selectively when intense motivational salience is processed, as in conditions that characterize psychopathological outcomes.
This demonstrates that the amount of norepinephrine produced in the prefrontal area of the brain correlates highly with abnormal reward responses that are often symptomatic in certain mental illnesses.

In other words, the abnormal brain produces an excessive response to certain stimuli in the form of higher levels of norepinephrine in the prefrontal cortex area of the brain, even when normal levels of norepinephrine are low.

Note that nowhere in this piece of the study does it state that this is a direct cause and effect. In the third bolded sentence, you can see that the authors acknowledge that there is a complex system at work, and that this experiment is testing only one potential mechanism of that.

However, by finding a connection between norepinephrine levels and psychopathology, it demonstrates that it might be possible to address these mental conditions with treatments that regulate levels of norepinephrine in the brain.

Oh, and just to make one detail a little clearer, the noradrinergic system refers to the process that creates norepinephrine. To state it simply, the adrenal glands produce adrenaline. The adrenalin that crosses the blood-brain barrier is converted to noradrenaline. Some of the noradrenalin is converted in the brain to norepinephrine.

Hope that helps.

daveddd
03-03-13, 11:25 AM
delayed reward processing problem , IMO?

intense interests, perseveration, "hyperfocusing", mania, all stem from the inability to regulate the drive for delayed reward attainment

Amtram
03-03-13, 11:35 AM
True, daveddd. Some dopamine in the brain is also converted to norepinephrine, so there are at least some chemical and synaptic ties between reward and aversion in the brain.

Drewbacca
03-04-13, 02:55 PM
Moderator Note: Several posts have been moved and/or edited for content that is inappropriate for this particular forum. The missing posts can be found in the Meditation and Spirituality (http://www.addforums.com/forums/showthread.php?t=141303) sub-forum.

Scooby Dude
03-04-13, 04:16 PM
I read this as saying that a CNS with abnormally low norepinephrine levels in the prefrontal cortex will NOT produce the normal motivational response to high stressors, positive or negative.

Thus, such a CNS might have a normal response to normal inputs (like casually watching a TV show) but fail to respond to a larger stimulus that should produce a more intense level of motivation (my paper is due next week and I need to start it tonight or else XYZ will happen).

The result is that for important (ie high motivational salience) activities, such a CNS needs to create an emergency, leading to a burst of adrenaline, to change the neurochemistry enough to function.

Essentially, such a CNS lacks the ability to react normally to a "normal-high" stimulus, and will either not respond at all, or else will need to create a fight-or-flight panic to respond.

Amtram
03-04-13, 06:51 PM
I suppose it would help to have access to the full study rather than just the abstract, if only for the charts. . .oh, wait - it's PLoS. I'll have to look at it in the AM before my brain poops out.

I was pondering that back and forth for quite some time while I was reading it, because it wasn't entirely clear. I'll have to correct that if I'm wrong!

mildadhd
03-05-13, 01:26 AM
Quote from the opening post research quote,.

Intense motivational salience attribution is considered to have a major role in the development of different psychopathologies. Numerous brain areas are involved in “normal” motivational salience attribution processes;




Motivation

Motivation is a psychological feature that arouses an organism to act towards a desired goal and elicits, controls, and sustains certain goal directed behaviors. It can be considered a driving force; a psychological drive that compels or reinforces an action toward a desired goal. For example, hunger is a motivation that elicits a desire to eat. Motivation has been shown to have roots in physiological, behavioral, cognitive, and social areas.
Motivation may be rooted in a basic impulse to optimize well-being, minimize physical pain and maximize pleasure. It can also originate from specific physical needs such as eating, sleeping or resting, and sex.
Motivation is an inner drive to behave or act in a certain manner. These inner conditions such as wishes, desires, goals, activate to move in a particular direction in behavior.

http://en.wikipedia.org/wiki/Motivation


Salience (neuroscience)

The salience (also called saliency) of an item – be it an object, a person, a pixel, etc. – is the state or quality by which it stands out relative to its neighbors. Saliency detection is considered to be a key attentional mechanism that facilitates learning and survival by enabling organisms to focus their limited perceptual and cognitive resources on the most pertinent subset of the available sensory data.
Saliency typically arises from contrasts between items and their neighborhood, such as a red dot surrounded by white dots, a flickering message indicator of an answering machine, or a loud noise in an otherwise quiet environment. Saliency detection is often studied in the context of the visual system, but similar mechanisms operate in other sensory systems.
When attention deployment is driven by salient stimuli, it is considered to be bottom-up, memory-free, and reactive. Attention can also be guided by top-down, memory-dependent, or anticipatory mechanisms, such as when looking ahead of moving objects or sideways before crossing streets. Humans and other animals have difficulty paying attention to more than one item simultaneously, so they are faced with the challenge of continuously integrating and prioritizing different bottom-up and top-down influences.

http://en.wikipedia.org/wiki/Salience_(neuroscience)




Attribution (psychology)

Attribution is a concept in social psychology addressing the processes by which individuals explain the causes of behavior and events; attribution theory is an umbrella term for various models that attempt to explain those processes.[1] Psychological research into attribution began with the work of Fritz Heider in the early part of the 20th century, subsequently developed by others such as Harold Kelley and Bernard Weiner.

http://en.wikipedia.org/wiki/Attribution_(psychology)

Amtram
03-05-13, 01:43 PM
Scooby Dude, it's even more interesting than that!

The mice were exposed to two rewards - they liked milk chocolate, but they LOVED white chocolate.

They were exposed to two aversive stimuli - they didn't like intermittent flashes of light, but intermittent flashes of pulsating light REALLY bothered them.

After being exposed to both kinds of stimuli, some of the rats were fed appropriate amounts of food, and some were fed a restricted diet to induce stress reactions.

The control mice showed maximum norepinephrine release in response to the white chocolate and the pulsating light flashes.

The stressed mice showed maximum norepinephrine release in response to the milk chocolate and solid light flashes.

When the mice had the norepinephrine artificially depleted, you're right, Scooby Dude - they stopped responding. All of them. So a deficiency in norepinephrine in the medial prefrontal cortex reduced the ability not only to apply motivational salience to the stimuli (responses to white chocolate and milk chocolate were similar, as were responses to both kinds of light) but to respond to stimuli at all with a release of additional norepinephrine.

To further test this, they exposed the mice to social isolation instead of food deprivation to see if the results would be similar. As with the first test, the artificial depletion of norepinephrine caused the animals to not have a preference for one kind of chocolate over the other, or avoid one kind of light more than the other.

(They also experimented with whether the depletion would affect the amount of chocolate or type of chocolate eaten - what they found was that the food restriction had an effect on the amount eaten, but not the amount of norepinephrine. Seems intuitive, but they had to be sure.)

The authors also mentioned that there are other mechanisms involved in connecting stimuli and reward/aversion and applying levels of salience (importance to the individual) besides norepinephrine in the medial prefrontal cortex, but that this shows a strong relationship between the two, and may provide the conditioning and memories that cause later salience of unconditioned stimuli. (Meaning. . .the norepinephrine release caused by the original stimulus is going to affect the reaction to later stimuli that the individual associates with the original.)

So. . .there's a lot of information in this study, lots that I didn't include here, and connections to other studies, but this is (as usual) a tiny piece in a much larger puzzle. However, this one's distinctive (maybe even an edge piece) and could help a lot in finishing one big section.

Conman
03-05-13, 01:57 PM
alls i know about Norepinephrine is that it's Epinephrine's goofy brother who regulates attention, sleep, learning and emotions (all to varying degrees of course since it works with others)

and apparently is also part of genetically linked 'imbalances' or 'deficits' in people who have AD/HD along with Dopamine and Serotonin (im not trying to make an argument about genetic or biological basis here, im just making a note)

Amtram
03-05-13, 02:14 PM
One of the interesting things in this study, Conman, is that hidden away in all that information is a mention that they also tested dopamine levels and found no variations in any of the mice!

Conman
03-05-13, 05:17 PM
wasnt paying much attention to the study itself since among other things, starting with an Abstract=massive-*** research paper

explain your comment

Amtram
03-05-13, 06:55 PM
NE depletion in the mpFC.

The effects of prefrontal NE depletion on tissue levels of dopamine and NE in the mpFC were analyzed by two-way ANOVA. The factors were as follows: pretreatment (2 levels: Sham, NE depleted), and experiment (2 levels: behavioral experiment, microdialysis experiments). Individual between-groups comparisons were carried out when appropriate by post hoc test (Duncan Multiple Range Test). Two-way ANOVA for the effects of prefrontal NE depletion on dopamine and NE tissue levels in the mpFC showed a significant pretreatment effect for NE only (F (1,189) = 2.23; p<0.0005) but no experimental effects. NE tissue levels were as follows: Sham group = 702±32; NE-depleted group = 71±13 ng/g wet tissue; Dopamine tissue levels: Sham group = 199±19; NE-depleted group = 189±16 ng/g wet tissue.

Moreover, it was previously shown that selective prefrontal NE depletion did not affect basal DA outflow nor DA outflow induced by pharmacological rewarding [27] (http://www.plosone.org/article/info:doi/10.1371/journal.pone.0003044#pone.0003044-Ventura2), [28] (http://www.plosone.org/article/info:doi/10.1371/journal.pone.0003044#pone.0003044-Ventura3) or natural aversive [41] (http://www.plosone.org/article/info:doi/10.1371/journal.pone.0003044#pone.0003044-Pascucci1) stimuli in prefrontal cortex of mice or rat, thus showing that NE and DA release is independent