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Yesterday’s piece on information and how it affects the endowment effect of hope might have been too philosophical for most readers, so today I am trying to give a neuronal substrate for the abstract idea of hope.

Hope is defined as: “To wish for something with expectation of its fulfillment.”

Hope is a very powerful force in humans. I think we can all think of examples – from the heroic to the everyday life.

Have scientist studied hope – not really but I will try to link several pieces of research to possibly shed light on the ‘power’ of hope.

Hope seems to be an energy source for humans. With hope we can walk across deserts, survive years under deplorable conditions in war camps, survive cancer, etc. Could there be a possible link between hope and energy? I know this sounds strange but give me the benefit of the doubt and read on (I am not proposing some metaphysical entity – or I don’t think I am).

In a previous blog piece I outlined to you how the D2 dopamine receptor plays a role in the energy efficiency of the brain (see also this post on your brain: it all comes down to energy and information). Blocking D2 decreases the brain’s energy efficiency.

Placebo effect and hope:

Now what is something close to hope that scientist study in the lab? I suggest at least one that is in the ballpark is the placebo effect.

The placebo effect is: the act of receiving a treatment (active or non-active) may produce a positive effect because of an expectation of a benefit.

That sounds a lot like the hope definition: “To wish for something with expectation of its fulfillment.”

(I didn’t even realize the two definitions were this close until I sought them out)

In humans there are real neurochemical changes when given the ‘sugar pill’ as we think we are getting the treatment and our brain changes due to this piece of information – thinking your are getting the treatment (see my information pieces, here and here).

One very impressive placebo study published in Science was (Fuente-Fernandez et. al., 2001) (I can’t believe it was that long ago I read that paper) in which a placebo given to Parkinson’s disease caused dopamine (DA) activation in the striatum and in a follow up study observed activation of the nucleus accumbens in the ventral striatum and concluded that it was this region responsible for the expectation of reward (Fuente-Fernandez et. al., 2002).

Placebo effect and pain:

Scott et. al., 2007 in a Neuron paper took a closer look at the placebo effect and subsequent pain response. The subjects were either given a pain medication or placebo (cross over study) and their brains scanned. The level of DA D2/D3 (the only reason the call it D2/D3 is because the molecule they use can bind to both the D2 and D3 receptor – but in general for this situation you can think of it as mostly the D2 receptor) activation in the nucleus accumbens (ventral striatum) region was correlated both with anticipated and experienced placebo effect (reduced pain). Next they added the anticipation of receiving money (the hope of money). For people that had a high placebo effect there was a very sharp rise in nucleus accumbens activation (DA – D2/D3) *as the money increased) and anticipation of receiving money (very similar to what was observed with the placebo effect). However, in the group that had less than normal placebo effect there was no rise in nucleus accumbens activation as the money increased ($ 0.20, 1.00, 5.00).

What this says overall is the higher the placebo effect in an individual the higher the nucleus accumbens activation along with the anticipation of winning/receiving money. Or to put it in reverse the subjects that had a higher response to money also had a higher DA D2/D3 activation of the nucleus accumbens, and greater reduction of pain when given the placebo.

This to me suggests that the higher the level of the DA D2/D3 system in the nucleus accumbens (many factors go into this including several polymorphic genes D2, DAT, COMT, etc) the higher ‘hope’ is. This is under the assumption that the anticipatory placebo effect is related to what we humans call hope.

Now taking this to another level – who do you think has more hope in society the ones at the top or the ones at the bottom?

Primate social hierarchy study and DA D2 levels:

In a landmark primate study (Morgan et. al., 2002, Nature Neuroscience) singly housed monkey brains were scanned for D2 binding capacity (n = 20). Next the primates were allowed out of their individual cages for the first time so all the animals were now together, and as you can guess a social hierarchy was formed. After a stable hierarchy was formed they re-scanned the primates brains. The high ranking animals D2 binding capacity increased by approximately 20% (the authors believe based on rat studies that singly housed animals have a lower than normal D2 levels at baseline, and therefore suggests that falling lower in the social hierarchy would cause a reduction in D2 levels if the animals start at a ‘normal’ baseline), however D2 levels in the low ranking individuals did not change. According to the early piece I wrote the lower ranked animals would have a less energy efficient brain.

What do you think – would you have less hope if you find yourself near the bottom of the social ranking – where you had less access to food and sexual partners?

To see if the changes in D2 levels had a functional effect in these animals they then offered the addictive drug cocaine to the animals. The high ranking animals with high D2 levels were resistant to addiction while the low ranking animals with low D2 levels were more addictive. These results are consistent with a large body of additional research that find low D2 levels is related with higher addiction rate.

Take home preliminary questions and message:

Is the level of DA and D2 in the nucleus accumbens a measure of hope (and brain energy efficiency)? Is there a direct link between your brain energy efficiency based on D2 levels and the amount of inherent hope in individual humans?

Several polymorphism can affect the overall activation capability of this system (DA – D2). But also environmental situation – such as lower or higher in social ranking can alter this system (along with potentially things like exercise). Does a loss of hope in humans cause a reduction in D2 levels (most likely temporary) similar to what happens with primates that are on the lower end of the social hierarchy?

We all know hope is a powerful force – how much hope do you personally have? Are individual differences in hope (and possibly persistence) related to DA – D2 levels?

And we have all been in situation when our hopes are on the up or down swing. We can go a long ways on hope – but also the loss of hope can be crushing. However, maybe a brain with high energy efficiency via high D2 levels may not only produce higher levels of hope, but also resist a decrease in hope after negative news or situation.

Okay here is my new (far as I know) biological based theory of human hope. Hopefully it will give you something to ponder this weekend.

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