This is an episode of the Frontier Psychiatrists Podcast. It’s a conversation between my Fermata team member, Chelsey, and Myself. This conversation is about us, at work, trying to understand neuroscience together. We recorded this one! An edited version of the transcript follows.
Owen Muir, M.D.: So we were chatting about the amygdala, and if you want to ask me any questions about it, I can answer them and edit it together. And that's a podcast.
Chelsey Fasano, BA: There's a lot of discussion in the field right now about location neuroanatomy or chemistry neurobiology. And I'm always thinking about how the two crossover, so we're talking about the up-regulation or down-regulation of the amygdala.
What are the neurochemical aspects of how the amygdala would be up- or down-regulated?
Owen Muir, M.D.: Neurochemistry is a great way of selling drugs and selling explanations that are easy to understand.
When we talk about neurochemistry, we're talking about a synapse between two nerves that are trying to communicate. There's a tiny little gap, and the way a nerve communicates with another nerve cell is a neurotransmitter is released from one and floats its way across a tiny little gap, and then hits a receptor on the other side, and that creates a change in that subsequent cell, which makes it either more likely or less likely to fire.
What's happening next is within that cell. There are intracellular changes that lead to an increasing likelihood of reaching an action potential and itself firing and effectuating the next change in its neighbor cells. We focus narrowly on neurochemistry, because we can look at and modify it.
We're getting obsessed with answerable questions— not with important questions. For example, we don't give people “hyper-glutamate,” the excitatory neurotransmitter in the brain. They'll have a seizure.
Those excitatory impulses open ion channels that cause immediate depolarization and firing of neurons. Uncontrolled depolarization leads to seizure and death. GABAergic drugs do the opposite thing. So, anything binding to the GABA receptor opens a chloride channel. Chloride's negatively charged.
And that changes the inside of the cell's voltage to negative, which means it's less likely to fire because you need more glycine and glutamate to increase the voltage. GABA is safe to agonize, because you're not going to get a seizure—but withdrawal is dangerous because now you're more likely to fire in the absence of the GABA drug.
We're focusing on other compounds like serotonin, norepinephrine, and dopamine, which functionally regulate the internal cellular environment, making firing more or less likely. And we focused on it because it's safer.
We got obsessed with what we knew we could do and not immediately kill somebody— as opposed to what might actually be effective or is happening naturally because, on their own, our cells are firing and releasing neurotransmitters and pulling them back up and regulating their voltage without us messing with it at all.
For example, the chemistry argument at the amygdala level is part of the story. But when we're talking about what information the amygdala is kicking out, it's really how fast it is firing. That's my kind of argument. It's a rhythm answer.
If we looked at the stage plot for AC/DC and saw they had a lot of cables and started worrying about which cable plugged into the guitar as opposed to they are going to play in time --and you can replace the strings, the guitar, the cables. You do not have a good AC/DC show if they play at a time, and if they're playing in time, even if the guitar cuts out like bass drums, Angus is still locked in, and it rocks.
We've focused on what's focused-on-able, not what matters.
Chelsey Fasano, BA: The primary neurotransmitters of the amygdala are precisely the ones you were talking about!
Owen Muir, M.D.: The n methyl D aspartate receptor is a binding site that modulates glutamine.
Chelsey Fasano, BA: So that makes sense as to why ketamine would strongly affect PTSD since it works primarily on NMDA and GABA. That would downregulate the amygdala, which would help to buffer against the overactivity associated with PTSD and subcortical areas.
Owen Muir, M.D.: The firing rate functionally comes down because each nerve in the amygdala firing becomes less likely by some amount.
Chelsey Fasano, BA: Is the feeling something to this whole hippie thing of vibration and vibe?
Owen Muir, M.D.: It's true at the level of the neurons in the brain. Yes. I think wavelength is an accidental term. I don't know. But it's the literal truth.
Chelsey Fasano, BA: We know that neural firing from some research that I've read affects motor movements and speech patterns, and so there probably is some truth to the fact that upregulation of specific circuits is going to cause speech pattern and motor movement differences that are going to be the bodily rhythmic reflection of the brain activity. We would pick up a vibe because we all sense those things about each other through our brains.
Owen Muir, M.D.: We're building a model of the vibe. I propose that a firing pattern represents everything in the brain. It's click click of one nerve group, right? And in the other person's brain, it's click click.
But in our brains, we build a model of our click. And then, we make a model with clicks in our neurons of the other person.
We're constantly building models of other people's minds in our minds with our pattern of firing. Then, we pick up signals from their motor movements and behavior. We're resynchronizing our model. with their model, and we're constantly just getting it a little bit wrong and getting back into sync, and what humans love is feeling in sync.
When we dance, we're dancing in time. Like the guy who dances badly, we find displeasure. When we dance together, we find it joyous. When we're dancing to the beat, we enjoy that because our brains all represent the beat simultaneously. We can look and see and feel with high bandwidth sensory cortex and high bandwidth motor cortex that we are together, and that lets us not bump into each other when we're dancing and emotionally not bump into each other's feelings when we're communicating.
The dopamine system, for example, which profoundly regulates ventral striatal activity around motor gating, is also implicated in not just motor gating but also the gating of behavior. Some of that behavior is our feelings, how we react to the feelings, and how we talk, think, or sing.
This is how we can do things like lie to each other politely and not get enraged. Because there are times when someone lies to you, and it's bad, and how dare you lie to me. There are times when someone says, thank you so much for calling. And we recognize that their thanks may not be sincere.
And both of us are definitely on the same page about that, but the underlying intent we have modeled for the statement is beneficent.
We're both on the same page about that metadata, which is, oh, the person's lying to me, but it's because they care and want me to feel good. And so I'm going to think this lie is kind in this context, and in other contexts, my internal model was that they shouldn't have lied as opposed to should have lied.
So it's not the lie; it's the intent that we model and can reconnect to that allows human behavior and motion. To go well. If someone's a lousy dancer because they have Parkinson's, you're not going to love it, even if you don't know they have Parkinson's, and you may feel more positively inclined to them if you understand they have a reason for it.
But it doesn't feel good. We feel good when we move together.
Chelsey Fasano, BA: We've had some discussions about this previously about you not valuing agreeableness or not liking that quality of when people pretend to be polite, and I tend to be more like that.
And I think when I do that. Often, when I attempt politeness or I attempt positivity, even in a situation where things feel pretty dire, and I don't think that way, what I'm doing, my intention, is I'm trying to slow down the dance. I'm trying to introduce something to the dyad that I'm a part of that is not necessarily totally authentic in that I'm not feeling it at that moment, but I want both me and the other person to handle it.
I desire. So, I create the desired state in affect, hoping the dance will move in that direction. It often works. If you fake it till you make it, and you choose grace, and you choose to give someone calmer and more positivity than you might feel like they deserve, they often follow suit by giving it back to you.
Owen Muir, M.D.: What mentalizing and Peter Fonagy would say about this is like the way to do that most successfully because some people will interpret it because their experience and trauma, for example, as a lie—an aversive lie— and that'll create mistrust, and they'll get agitated, right?
Like, how dare you be polite to me, right? For those individuals and people who like politeness, you can do the same thing: mark your intentions. I'm going to be polite now. It's just that much—set it up. “I am behaving in a way because I hope it will be helpful.”
You can tell me if that's different from how it comes across. You can do whatever you want, and you have the spoonful of acknowledging the rationale for your behavior that gives them the additional information that you're doing it within the intent of XYZ, as opposed to just being polite. They can assume you're scamming them with your politeness.
Because they're people who've been harmed, scammed, and traumatized by polite people who wanted to abuse them. Thus, politeness for them may be a signal of risk. And so it's the ability to mark that I wonder if politeness is the right way to go, but I will try it out. That is the kind of permission slip to behave; however, you need to behave and also eat if it goes poorly… in a tolerable way.
“Wow, my politeness came across badly there. I can see by the look on your face that politeness was the wrong approach,”
Then suddenly, they feel understood and don't want to argue with you anymore.
Chelsey Fasano, BA: We've talked before about having a mini version of the other person in your head, which, according to this conversation, the mini representation of the person that we have would be not only our conceptions of them and abstract representations but be a literal rhythmic firing of neurons, which explains sort of emotional contagion and how you can feel someone else's feelings.
Owen Muir, M.D.: Mirror neurons are a metaphor for mirror patterns of circuits firing
Chelsey Fasano, BA: When we're looking at different schools of therapy, and some people are saying all of the feelings that you're feeling are definitely counter-transference are all coming from your past. It sounds like what you're saying is that's not accurate. What is happening is that we're getting rhythmic representations of the person that are combining with the conceptions that we previously had of what those rhythmic representations mean to create a sort of mini person inside of us that then informs both Our immediate affect as well as our ability to predict another person's behavior across time.
Owen Muir, M.D.: a million percent correct. So it's yes. Therapy is neuromodulation using the sensory experience of another plus the representation they have of us and the representations we have of them, and the desync/resync on repeat —is what therapy is. If you've seen projective identification when you come across that term, the ability to invoke in another person Psychodynamically a behavior that's true because of my ability as a human to create a model of you and perturb that model and react to the perturbances. I see it in a way that's in keeping with my internal representation.
It's a fish swim in schools. They're not sending a letter to all the other fish in advance, being like, okay, so in second 17 — turn left. They're modeling all of the other fish and then swimming in context with the model and then adjusting the model in each fish, so there's the constant adjustment of how much the school is moving because we're all building models of the school and checking them with each of the nodes in the network.
In therapy, you have a dyad that's doing the same thing. I move left, and I expect you to move right, and you move right as far as you move right. And then that hits or doesn't hit the model I have, and then we move back to the center and do it repeatedly. That's the misunderstanding that is the neuromodulatory agent in psychotherapy. Still, it's brain rhythms in both people's brains firing and then checking, and error checking against the visual sensory interpretation as presented to consciousness and heavily edited by subcortical structures that make that dance happen. It's the getting it wrong, just like in meditation, -- we're attending, losing the attention, bringing it back to the flame. And bringing it back to the flame is why we meditate, not simply “staying on the flame.” It's supposed to be challenging.
It's better if it's hard because it's a workout. -- Therapy is better if it's hard because it's a workout. But it's not just for attention regulation; it's a process of re-syncing to better inter-human and intra-personal things because when you do it in therapy, you get to do it out in the world when the therapist isn't there to help. So, being a therapist who's a little bit wrong all the time and then gets back to it is the honest answer. Ta-da! How's that?
Chelsey Fasano, BA: Good.
Owen Muir, M.D.: Let's see if it turns into anything.
The Neuroscience of Fear