It’s the Salient Detection System, Stupid

 Can you tell the difference among pain, depression, and pleasure?

From a neurotransmitter perspective, the answer is no (see here and here).

How is it that three very different states can be so neurologically similar?

I feel the commonality that the nervous system purports reflects a system that responds to stimuli that are deviations from the norm. We call these instances by this word:

Salient.

Doesn’t that make your loins quiver?

Let’s discuss how it works. Here’s your recommended reading.

1. The pain matrix reloaded: a salience detection system for the body (Thanks Sigurd)

2. Stress signalling pathways that impair prefrontal cortex structure and function (Thanks Son)

3. From the neuromatrix to the pain matrix (and back)

[Note: Most of this article is an amalgamation of the three articles that I cited above and my own thoughts. Rather then cite every sentence AMA-style, I’ll give the credit to these guys above. Read ‘em and figure out how I put this together. For those who are sticklers for proper reference formatting, the type I am using is KMA-style citation.*]

The Pain Neuromatrix Myth

Hate to break it to you, but pain ain’t so special. Here’s why.

If you follow modern pain science, you may often hear the term pain neurosignature or neurotag. This phrase is meant to describe a cluster of brain areas that are active during a pain experience.

Information that can contribute to a pain experience travels to several areas. Some of the big players are the primary and secondary somatosensory cortices (all the talk about the homunculus), the anterior cingulate cortex (ACC), and the insula to name a few. These bad boys are consistently active when pain from a nociceptive stimulus occurs. Hence, these brain areas are considered to be part of the pain neurotag present in us all.

However, this theory has a couple problems. First off, there is no brain area that exclusively responds to nociceptive stimuli. That includes the aforementioned locations.

In fact, these areas have been shown to simultaneously activate by the following sensory inputs: nociceptive, somatosensory, auditory, and visual. This variety can be explained by the vast array of wide-dynamic range neurons; neurons that carry multiple inputs to cortical areas.

The suggestion: the supposed “pain neuromatrix” can respond to a wide variety of sensory inputs. I don’t think the input matters much at all. This fact takes the quote “nociception is neither necessary nor sufficient for a pain experience” to a completely different level. I like this instead:

 “Any input is not necessary, but sufficient for a pain experience.”

As if pain wasn’t complex enough.

[Interesting side note: nociceptive specific neurons have been shown to be active when a threatening visual stimulus occurs. How many of you folks who treat pain are asking about vision? Maybe there is something to that PRI after all.]

So how is the pain neuromatrix demolished? Because of the first point I mentioned in this post. We could also see a wide variety of outputs that neurologically appear similar to pain occur. The neurosignature is not always exclusive to pain.

Let’s rephrase our quote again.

“Any input is not necessary, but sufficient for any output.”

What would constitute a change in output that resembles what was once thought as the pain neuromatrix? Here is where salience comes into play.

The Salient Detection System

A salient stimulus is something that stands out relative to the background. The intensity is irrelevant; the key is how different the input is. These inputs can occur within the body or the environment.

An elephant in a room is salient. A room full of elephants is not.

But here is a more scientific example. One study mentioned in the articles used a monotonous nociceptive laser stimuli interspersed with a novel nociceptive stimuli of various physical properties. Larger activity in the “pain matrix” areas occurred when the novel stimulus was applied, regardless of how intense this was.

 Deviation from norm is what is necessary for this system to activate. Let’s upgrade our phrase again:

 “A salient input is necessary for an altered output.”

Being able to respond to salient inputs helps one adapt to environmental and body changes. This is why nociception can be powerful, as it is a very salient stimulus.

Because there are no brain areas that respond exclusively to nociceptive stimuli, the brain areas typically involved in “the pain matrix” are more likely involved in an all-encompassing salient detection system. The outputs that occur are the brain’s best guess at how to adapt to this new stimulus. As to why one output may occur over another is likely beyond our current knowledge base.

It Comes Down to Threat

If you haven’t read before, I believe that stress/threat that goes beyond our system’s capacity (i.e. is salient) is ultimately what leads to many of the outputs we see clinically.

Let’s see this process in action. Let’s suppose you are exposed to a threatening salient stimulus.

When a severe stressor occurs, the prefrontal cortex (PFC, our decision-making center) decreases its activity and the amygdala takes over. The amygdala likes predictable behaviors, so habitual strategies will run to combat this stressor. This is the stuff you are good at.

If the PFC is active, we consider that top-down control. When exposed to a threatening salient stimulus, bottom-up processing via the amygdala is more dominant.

Stress and inflammatory hormones flooding the system compound this shift, which strengthen the amygdala and weaken the PFC.

Getting Stuck in the Cycle

Let’s suppose you are exposed to a threatening salient stimulus and are fortunate enough to survive. Your brain will ask the following question:

“How do I prevent that from happening again?” ~ Your brain

The major players here are dopamine and norepinephrine.

Whatever output was successful in threat attenuation will be positively reinforced by the amygdala. Our reward neurotransmitter known as dopamine increases its presence when a stressor is applied. Outputs used during that stressful situation will be captured and rewarded for occurring. Over time, this process can contribute to chronic outputting (pain, addiction, PTSD, etc).

If pain fear-avoidance reduces threat, reward. If anxiety keeps you protected, reward. If snorting a mountain of coke keeps you happy-go-lucky, reward.

To me, the above outputs are the same thing. The outputs that become chronic depend on if maintaining chronicity ensures one’s survival.

Norepinephrine, our neurotransmitter that gives us that adrenaline rush, initially drives us sympathetically to combat that threat. However, in chronic stress environments such as those mentioned above, norepinephrine will begin to fire to irrelevant stimuli. These changes can now make inputs that were once nonthreatening threatening.

Going from Vicious to Delicious

So we are stuck in a bottom-up amygdala-happy cycle. How do we get out of it? PFC is the hero we deserve so we can hope to stimulate top-down activity.

We have a problem though. When we have a chronic x, y, or z, working memory over-attends to inputs that perpetuate said output. It takes over our working memory. Individuals stuck in a chronic cycle have a hard time getting out of this state because the output occupies the mind and is rewarded by dopamine.

There’s only one way to break the cycle: Salience.

A new, favorably salient input is necessary to encourage top-down processing. This is how our rehabilitation process begins.

Introducing a favorably salient input is only step one. This piece provides a window of opportunity for learning a new strategy, as the previous threat is reduced.

That’s why manual therapy must be incorporated with exercise. That’s why achieving neutrality is only step one, that’s why therapeutic neuroscience education stops benefitting after 3 months. That’s why a joke is less funny after the first time its told.

These examples are the same. All are novel stimuli that divert attention for a brief moment in time.

And they won’t work forever.

[Side note: 2 Batman + 2 Outkast references = best blog yet]

When the system is flipped to top-down, one must introduce variability, capacity, and/or power to better attenuate future threatening inputs. When an individual’s sweet spot of these qualities is found, better stress management occurs. Those salient stimuli that push someone into an unfavorable bottom-up cascade are no longer salient.

The standouts just become part of the noise.

Last Remarks

We now have a neurological framework for which we can treat individuals who are under threat, and the common link among all these folks is salience. Recognizing what salient detection means, and creating better body-spatial environments to combat threatening salient inputs, may be a major factor in reducing some of the chronic conditions we see.

Now that’s a cool system…

 

 

 

*KMA = Kiss my ass**

** Granny would be proud