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WHAT INVESTIGATING NEURAL PATHWAYS CAN REVEAL ABOUT MENTAL HEALTH

15.07.21

WHAT'S IT ABOUT?

Overview from TED

Neuroscientist Kay M. Tye investigates how your brain gives rise to complex emotional states like depression, anxiety or loneliness. From the cutting edge of science, she shares her latest findings - including the development of a tool that uses light to activate specific neurons and create dramatic behavioral changes in mice. Learn how these discoveries could change the way you think about your mind - and possibly uncover effective treatments for mental disorders.

"In the near future, I expect to see a mental health treatment revolution, where we focus on specific neural circuits in the brain. Diagnoses will be made based on both behavioral symptoms and measurable brain activity."

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Kay M. Tye

Neuroscientist

Kay M. Tye investigates the neurobiological mechanisms underlying social and emotional processes, particularly those relevant to psychiatric disease. She is the Wylie Vale Chair of the Systems Neuroscience Laboratory at the Salk Institute for Biological Studies, where she is also a member of the Kavli Institute for Brain and Mind. Tye currently serves on the Board of Scientific Counselors for the National Institute of Mental Health.

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MY TAKE...

I’m in two minds about this talk. On the one hand, any innovation that can potentially improve the mental health of millions is inherently valuable. But is the manual manipulation of neurons within the brain a step too far?


Kay M. Tye’s hypothesis is clear: That making a very specific change to neural circuits in the brain can result in specific changes to behaviour. That every conscious experience we have is governed by cells in our brain.


This is undoubtedly an important area for scientific discovery, especially given the disparate treatment of physical and mental illnesses. But is routine brain surgery really the answer to anxiety, depression and a plethora of other mental health issues? Where would we draw the line? And at what cost?


In the ever-wise words of Jurassic Park’s Ian Malcolm, “[Your] scientists were so preoccupied with whether or not they could, they didn’t stop to think if they should”.


Tye makes comparisons with mechanics looking under the hood of a car. The analogy makes sense, except that the brain isn’t a faulty part that can be easily taken out, tinkered with or replaced. I find it difficult to believe that the reprogramming of neural circuits could not have unwanted side effects. And I’m not talking about the success rate of surgeries, but the long-term impact on motives, desires and personality.

THE JOY OF FOOD

Tye’s example focuses on over-eating, something I’m sure we’re all guilty of from time to time. But when that behaviour becomes compulsive, what can be done about it? According to Tye:


“We can eat for two reasons. Seeking pleasure, like tasty food, or avoiding pain, like being hungry. How can we find a treatment for compulsive overeating without messing up the hunger-driven feeding that we need to survive? The first step is to understand how the brain gives rise to feeding behaviour. This fully-fed mouse is just exploring a space completely devoid of any food. Here we're using optogenetics to target neurons living in the hypothalamus, sending messages down wires aimed at the midbrain. When I turn the light on, right here, you can see that the mouse immediately begins licking the floor.”


She continues:


“This seemingly frenzied behaviour is about to escalate into something I find really incredible... he picks up his hands as if he is eating a piece of food, but there's nothing there, he's not holding anything. So this circuit is sufficient to drive feeding behaviour in the absence of hunger, even in the absence of food. I can't know for sure how this mouse is feeling, but I speculate these neurons drive craving based on the behaviours we elicit when we target this pathway. Turn the light back off - animal's back to normal. When we silence this pathway, we can suppress and reduce compulsive overeating without altering hunger-driven feeding.”


Food for thought. But surely applying such treatment to human beings is a different kettle of fish entirely? By suppressing the urge to overeat, how can we be sure that the enjoyable side of eating isn’t impacted too? The pleasure of sharing a pudding with a spouse at an anniversary dinner, or breakfast in bed during a weekend away... If eating is purely a functional exercise, where is the joy?


And it doesn’t stop there.

STRESS TO IMPRESS

Tye’s other example focuses on anxiety, utilising an “elevated plus maze” (a structure with four arms in the shape of a cross) to track a mouse’s behaviour. Tye explains:


“Mice have evolved to prefer enclosed spaces, like the safety of their burrows, but to find food, water, mates, they need to go out into the open where they're more vulnerable to predatory threats… now, when I flip the switch and turn the light on, you can see the mouse begins to explore the open arms of the maze more. And in contrast to drug treatments for anxiety, there's no sedation, no locomotor impairment, just coordinated, natural-looking exploration. So not only is the effect almost immediate, but there are no detectable side effects.”


Again, this is a huge breakthrough for science but is it a practical solution to tackle anxiety-driven behaviours in humans?


Consider this: you’re about to give a presentation to more than one hundred people. Your palms are sweaty; your throat feels dry. You haven’t slept properly. You feel your cheeks reddening as you approach the podium, and your fingers tremble as you fumble with the presentation clicker (unless you’re Chris “Next Slide” Whitty of course!).


Given the opportunity, I expect you’d jump at the chance to “switch off” your anxiety in that moment; perhaps turn off anxiety permanently. But it’s not a given that eradicating anxiety is the best course of action.


Studies have shown that anxiety can actually help in certain situations. Not only can our innate fight or flight response protect us from harm, but anxiety can also improve our performance. As an article from Talkspace explains:


"When faced with a challenging client meeting, a public speaking engagement, or a big event, anxiety serves as a natural checkpoint for honing in our focus and achieving our goals. This hyper-arousal and adrenaline rush often slows the digestive tract to make all biological processes work together to ensure success. Anxiety often comes to the rescue when it’s crunch time.


"Research shows that students and athletes with some anxiety displayed improved performance on tests or while participating in competitive sports. Another study found that people who have good memories and who get anxious do better in exams.


"But according to the Yerkes-Dodson Law, there are limits to the positive impact of anxiety on performance. Performance increases with arousal, but only to a certain extent, when anxiety begins to hinder. Think of a wedding where the best man could only muster a few words, or when completing a standardized test was impossible as your heart beat out of your chest. The key is keeping anxiety levels in check to capitalise on its positive impact."


The last sentence is particularly important: The key is keeping anxiety levels in check to capitalise on its positive impact.


If neural pathways could be reprogrammed in a less black and white way (i.e. reduce anxiety rather than turn it off altogether), the impact could be monumental. It could provide a much-needed lifeline for those who need it most; an opportunity to operate in a healthier, more balanced way without the need for life-long medication.


It’s still early days, but I’m excited for what comes next. Not least, the shift in perception that Tye hopes will follow:


“If from this very moment forward, each and every one of you left this talk and truly believed that the mind comes entirely from cells in your brain, then we could immediately get rid of negative perceptions and stigmas that prevent so many people from getting the mental health support that they need.”


She concludes:


“[As] Mental health professionals, we're always thinking about what's the next new treatment. But before we can apply new treatments, we need people to feel comfortable seeking them… When we truly understand exactly how the mind comes from the brain, we will improve the lives of everyone who will have a mental illness in their lifetime - half the population - as well as everyone else with whom they share the world.”

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