Rhonda: I remember reading somewhere, too, that isn't the, like, amygdala, like hyperactive or something happens, there's not an inhibitory signal that occurs if you're sleep-deprived or...?

Matt: That's right.

Rhonda: Is that correct?

Matt: Yes.

Rhonda: So then you're feeling more...you're, like, alarmed and, you know, just anxious and feeling that in a, say, threat...

Matt: That's right.

Rhonda: ...that ongoing threat that really isn't there.

Matt: Exactly, yeah. So we published the study in 2007 where we, again, sort of sleep-deprived people, put them inside an MRI scanner, and we showed them increasingly negative and aversive and unpleasant images. And what we saw is that, relative to people who'd got a full night of sleep, the amygdala, this sort of emotional epicenter for the generation of strong, emotional, impulsive reactions, that deep emotional center was 60% more reactive under conditions of a lack of sleep.

And then we asked why. Why is your emotional brain so sort of sensitive and erupting with such extraordinary activity? And what we then went to find, or went on to find out in later work, was that another part of your brain called the prefrontal cortex that sits directly above your eyes here, and particularly the middle part right between your eyes, that part of the brain acts almost like the CEO of the brain, of your emotions, and your hedonic impulses. And it sends sort of an inhibitory top-down regulatory control. It's sort of, like, the brakes on the gas pedal of your emotions.

That part of the brain was shut down by sleep deprivation, and you'd lost that communication to the amygdala. So now you, from an emotional standpoint, you were all emotional gas pedal and too little regulatory control brake as it were.

Rhonda: It's really interesting. This work kind of reminds me of...I'm not sure if you're aware of any of this research. A lot of it has been done by Dr. Molly Crockett, who, I believe, now she's at Harvard. But she has done a lot of studies looking at serotonin depletion in the brain. And basically, you can induce that by giving acute tryptophan depletion, giving someone like branched-chain amino acids to compete with transport for tryptophan in the brain, which then basically drops serotonin levels. I mean, you can drop your serotonin levels down to, like, 10%.

Matt: And mood is...

Rhonda: And the same thing happens where, exactly what you were describing, the inhibitory signal that happens from the prefrontal cortex onto the amygdala is, like, stops. And so people become extremely impulsive. Terrible moods, a little more aggressive, their long-term planning shuts down, and they just, like, going for the short-term gratification. Very similar. So it'd be kind of interesting...I don't know how serotonin would be related to all that, but there must be some sort of connection.

Matt: Yeah. I mean, and I think there's a number of different, I think, neuro chemicals that can produce that same kind of neural phenotype and as it were. But what struck me was that when I looked at that neural signature of sleep deprivation for the emotional brain, it was not dissimilar to numerous psychiatric conditions. And that then now, gosh, 11 years ago, I'm showing my age, but that set sort of, you know, the sleep center off on a completely new trajectory of work. And we're doing a lot of this work in sleep and psychiatric disorders.

And I think one of the most fundamental things that I can say at this point is that we have not been able to discover a single psychiatric condition in which sleep is normal. And so I think sleep has a profound story to tell in our understanding, maybe our treatment, I don't know about prevention, but possibly, of grave mental illness. And psychiatry has known this, by the way, for, you know, 40 or 50 years. It's always been documented that sleep disturbance goes hand-in-hand with psychiatric disturbance.