Some patients with Parkinson's disease can tap into a "back up system" in their brain to stay motivated, according to a new study which could pave the way to new treatments and understanding of the condition.
Scientists at Dundee University set out to compare 75 Parkinson's patients with and without clinical apathy - one of the first and most prevalent symptoms - by studying their brain activity in an MRI scanner while they took part in a computer game-style challenge.
An additional 22 matched volunteers without Parkinson's were recruited as healthy controls.
Participants were asked to obtain as many points as possible by choosing between four options.
As the game progressed, the value of each option changed in a similar way to the fluctuations of the stock market meaning that they had to repeatedly decide whether to stick or switch.
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Those diagnosed with clinical apathy were able to identify the best option but tended to give up on it prematurely, moving on to a different one despite it being potentially worse.
In contrast, those without apathy were able to track the best option as well as healthy participants.
When the scientists studied brain activity, they discovered increased activity in a "back channel" within the brain among the Parkinson's patients without apathy suggesting that this area was being effectively "reprogrammed" to maintain motivation levels.
Dr Tom Gilbertson, who led the study, said: "In the context of apathy in Parkinson's disease, no one had really appreciated prior to this study that there was another circuit that brain could use to maintain motivation.
"It's quite a unique observation."
Apathy can often be mistaken for depression, but while people with depression can feel pessimistic about their future, those considered apathetic feel indifferent and unmotivated.
Dr Gilbertson, a senior clinical lecturer and honorary consultant neurologist at the university's School of Medicine, said the findings - published in the prestigious medical journal Brain - could lead to new treatments that significantly improve the quality of life of people living with Parkinson’s disease.
He said: “People with Parkinson’s who develop apathy have a much poorer quality of life.
“That includes an increased likelihood of developing dementia and being less likely to respond to treatments that are normally highly effective including surgery.
“They are less incentivised by decisions and actions that could lead to rewarding outcomes, which in the real world could see a person being less likely to seek social interaction or pursue a hobby they have enjoyed.
"That is because their brain does not embed information about what is valuable, and losses its ability to remind a person of what is worth doing to achieve a goal.
“This is the first study to show that the brain can, even in a diseased state like it is with Parkinson’s, override this loss of this function.
"Understanding the mechanisms behind this compensation could help us develop new treatments aimed a treating or preventing apathy to transform quality of life for patients.”
The section of the brain which lit up in the non-apathetic Parkinson's patients connected the thalamus to the pre-frontal cortex.
It remains unclear exactly why some patients can generate this response, but Dr Gilbertson believes it could be biochemical.
Other studies have shown that, over time, declines in hormones associated with brain reward systems - serotonin, noradrenaline, dopamine - correlate with apathy onset in Parkinson's.
Dr Gilbertson said: "One possibility is that the first thing you lose to some degree is dopamine into frontal lobe - so that's the first 'hit'.
"It could be that this other circuit we've identified is up-regulated by other neuro-modulators like serotonin and noradrenaline, and when they're lost - it's the patients who've had this 'double hit' who actually manifest apathy.
"But that's entirely speculative at the moment."
If the hypothesis stacks up, Dr Gilbertson said it could open the door to using existing drugs - such as antidepressants - as an early intervention.
He said: "One of the things we've started to study are groups of patients in the community who are on SSRIs [selective serotonin re-uptake inhibitors] to measure their levels of apathy.
"We don't find much in terms of apathy in those patients and I think one of the treatments for Parkinson's might be using drugs that are already out there, like [SSRI antidepressant] sertraline, to prevent the progression to apathy.
"If we're correct - and we still have a lot of work to do to prove that serotonin is what's driving this compensation in the brain, and that SSRIs are not bad for apathy - then, potentially, it means we've already got a drug out there.
"That if you put someone just diagnosed with Parkinson's who doesn't have apathy on something like sertraline, you may delay the progression to apathy in the future.
"That would be fantastic to test in a clinical trial, but we're still a long way off from doing that."
Another unanswered question is whether stopping or delaying the onset of apathy would also slow disease progression and extend survival.
In PSP - a rarer Parkinson's-like disease - development of apathy has been shown to be highly predictive of how much longer a patient has to live, suggesting that it has a disease modifying effect.
However, Dr Gilbertson said this is less clear for Parkinson's disease.
He said: "We don't know the answer to for Parkinson's. If you can treat apathy in PSP, you could potentially delay death. In Parkinson's there isn't evidence for that.
"But quality of life is really important, which is why everyone is desperately trying to find a better way of preventing it and reversing it if we can.
"The big question for me is whether or not it's reversible. It might be that once the degenerative process has knocked out all of those scaffolding layers [in the brain] that you cannot reverse it.
"But we won't know until we've investigated that."
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