So I'm gonna tell you about some research we're doing at Mount Sinai.
Also on habituation using a psycho physiological approach called startle eyeblink effect of startle modulation.
So we know and actually, I'm gonna qualify myself, I'm actually one of those non clinicians here. And I'm really enjoying this meeting. And I do want to thank Mary and the program committee, I've actually learned a lot. I'm really a cognitive neuroscientist, so, but I do study borderline personality disorder with my colleagues at Mount Sinai.
So I'm telling you things that you already know. So you're going to have to forgive me, we know that borderline personality disorder has a high suicide rate. And we know that patients with borderline PD utilize more mental health resources than individuals with other psychiatric disorders. And we also know from work such as the work that Harold just presented, that they do show an excessive reaction to emotional stimuli. So I think it's important to understand the core psychological processes that underlie the features of borderline personality disorder that lead to negative outcomes. And I'm trying to do this using some psychophysiological techniques.
We know that aspect of instability, as Harold just reminded us, is the most prevalent and enduring diagnostic criteria for borderline personality disorder. And it's also the most enduring over time, as you can see from this landmark study by McGlashan at all, it's at the top of the list here, and a follow up effect of instabilities at the top of the list in borderline personality disorder. So how do we define emotion dysregulation?
Well, from a psycho physiological perspective, the work of Marsha Linehan is really perfect. So emotional dysregulation is defined, or characterized by an inability to regulate emotional responses with a high sensitivity to emotional stimuli. And those could be unpleasant or pleasant, and an unusually strong and long lasting reaction.
So if we imagine for a moment that we have an emotional stimulus in this case, let's say that it's an unpleasant stimulus. In healthy individuals, if we're looking at a psycho physiological response, such as the startle eyeblink response, which I'm going to tell you about, in a few moments, we would see a response to that stimulus.
So here's our healthy control response. In borderline personality disorder, we would imagine that that response would be a higher amplitude, or higher peak, and then it also might have a slower recovery down to baseline.
Additionally, if we presented that emotional stimulus again, and repeated it, in healthy individuals, we would imagine a decrement in the amplitude of that response is Harold, just to talk just discussed and Marianne talked about yesterday, post DBT treatment, whereas in BPD patients, we might imagine that they would show a greater amplitude or deficient habituation in processing this emotional stimulus. So deficient habituation to repeated stimuli as per Marshall enhance, really nice conceptual model.
So we first looked at this similar to Harold's work presented today we looked at this, as Maryann talked about yesterday, briefly, in the fMRI environment, using these international aspect of pictures, show pictures, which are all rated, and there's a manual, some people use manualized treatments, I use manualized pictures in my experiments. So we repeated the pictures in the magnet, they were presented for six seconds. And this allowed us to look at the bold response to repeated picture processing.
We also told the patients and the healthy controls in the study to think about the meaning of the pictures for them personally. And I also do want to add in that we use social pictures, because we know that that's important in studying borderline personality disorder. Additionally, the little icon there that you see the little noise, or excuse me, sorry about that. The little speaker is reminding me to tell you that we actually on half the trials, presented a very brief burst of static.
The idea here is that I was trying to make this fMRI experiment as similar to what I do in the psychophysiology Lab as possible. It turns out that the little noise bursts really didn't affect the fMRI data. But as we're going to get to it does affect psychophysiology data. So in the fMRI experiment, we traced the amygdala in each of the participants wind to diagnosis, which was very heroic effort by one of my graduate students, and we co registered it to their bold response.
And Maryann showed this data yesterday. I'm just going to remind you about it.
What we saw is overall average overall the picture types, the BPD patients showed a delay Their response, coming back down to baseline, and that you can see with the green arrow. Additionally, when we broke out the trials into novel and repeat, as Harold just talked about, we saw an increase in the amygdala response. I'm focusing on the amygdala, I apologize, I am very amygdala centric, I'm going to get to why I think that's important, a little later, because it's very translational and animal models often look at the amygdala. So here we are showing you that a bigger response in the BPD patients to repeated pictures. And that's this has averaged over all the picture types.
However, it's important to know that two thirds of them were the emotional pictures, the pleasant and the unpleasant pictures, 1/3 of them were novel.
If we further parse it out into unpleasant neutral and pleasant types of pictures, we see with the blue arrows, that really, the the effect here is that the borderline patients show an increased amygdala response to both unpleasant and pleasant pictures.
And interestingly, these pictures are matched on arousal level, they're highly arousing. And they differ from the neutral pictures, which are low on arousal. So this suggests that the BPD patients have an overall arousal deficit, not a valence deficit in this case, because they're showing this abnormal habituation to both unpleasant unpleasant stimuli.
Here's a brain picture for those of you that like brain pictures showing you and actually john Gunderson, I hope he's still here should like this, because this shows the specificity of this effect.
It's the amygdalas hire, to repeated unpleasant pictures in BPD, but not in in patients that have schizotypal personality disorder. So some specificity. Interestingly, when we look at their self report, they rate the pictures on a nine point scale. And we find something similar to what Jill huli presented yesterday, we find a mismatch between what they say about how the pictures made them feel, and what their amygdala was telling us. So their amygdala is jacked up. But on self report, they're showing a blunted response. As you see on the left here, the BPD patients are lower in saying that the pictures really weren't that bad compared to healthy controls.
Similarly, they think that the pleasant pictures on the right side are more unpleasant compared to the healthy controls. So a dissociation between their physiology and their self report, which is consistent with this idea of alexithymia. So now, we're going to turn to psychophysiology. And I'm going to try to be a little bit of a salesperson here, I'm going to tell you why I think psychophysiology is really cool.
So some of the advantages of psychophysiology are that it's very easy to record and clinical populations. So here is actually a happy research assistant in our lab, who's now in graduate school, showing how we put these little recording systems under the eye one goes behind the ear, and they sit in a nice quiet room and they see these pictures on a computer screen, the experimenters outside the room, but keeping a close eye on them. Secondly, it psychophysiology or affective startle in this case is a great way to get a nonverbal, very objective measure of emotion, we're not asking them anything, we're just simply having them experience this paradigm.
We do actually afterwards ask them to rate the pictures, they view them again, and they rate them. This shows you how we record non invasively we put these recording discs under their eye we record from the killer slackline muscle. And we're not asking them anything.
Mapping this on now to Peter Lange's theory or model about by phasic emotions. What happens here is when you see an unpleasant picture, which is the very top stimulus, and five seconds into this unpleasant picture, we present a very brief burst of static through some headphones, 50 milliseconds 100 decibels, it sounds like a click, we elicit a blink response, which is part of the whole body startle response. And we get a rather large amplitude on this blink response. So according to Lang's model, this is an aversive defensive emotion. It's an unpleasant picture, and superimposed on that it's sort of an immersive, startle stimulus. So the blink is enhanced.
In contrast to that, if you're looking at a pleasant picture, and you present the startle probe, you see an inhibited response. This is appetite of repetitive emotion. The startle response is diminished. Because in this case, you have a pleasant experience and you're presenting the unpleasant startle acoustic probe, and it's diminished in terms of your physiological response. And the response to the neutral pictures is intermediate. This has been shown in labs across the country, really 1000s of experiments a lot with like 100 students, you get this beautiful stepwise pattern with big amplitude the unpleasant stimuli small amplitude to pleasant and neutral being intermediate. Another great advantage of this aspect of startle is that it's translational. So everybody that's a mammal shows the startle response, making it nice to translate across animal and human models.
Here you see the armadillo jumping up in the air from the National Geographic photographers flash. And the humans, we often are startled physically in show the whole body startle. So in rats, we record this. Actually, others record this using a potentially ometer and measuring whole body startle. And in humans, we use the hyperlink component.
Very quickly, the startle pathway itself is a very basic pathway that I'm not particularly interested in. But what's of interest to us in terms of studying emotion is that it's regulated or modulated by the amygdala. So the amygdala has a top down influence on the brainstem modulating the amplitude of the mind response in this case. So increased amygdala activation leads to enhanced startle response.
Lastly, aspect of starless potential biological endophenotype. It's also perhaps, a good adjunct, I'm going to try to convince you today for maybe looking at patients pre and post therapy as Marian Goodman is doing. So the startle paradigm is very similar to the fMRI paradigm I showed you a few minutes ago, pictures are presented. And the little gray arrows that you see.
I don't have a pointer, I apologize, are the startle probes that are presented sometimes during the pictures and sometimes in between the pictures, and we measure the amplitude of the blink response. So I'm going to present some data on a sample of 30 healthy controls 35 patients with borderline personality and 26 patients with schizotypal personality disorder. They were matched on demographics.
We were very rigorous about diagnosing them in the in the mood NPD Group with Larry Seaver and Antonia new. Here's a little bit about their some of their self reports. I realized this morning when I was looking at the slide that the healthy controls here have a high STI STI score, looking like they're anxious. I mean, they are New Yorkers. But I think that could be a typo. I'm gonna have to check that before I submit this paper.
But basically, the borderline patients couldn't have more than three SPD traits. And the spds couldn't have more than three BPD traits. In many ways, the schizotypal are sort of opposite Harold uses avoidant personality disorder as a control psychiatric control group. In this case, I use schizotypal personality disorder because I'm actually interested in schizophrenia Spectrum Disorders as well.
So you can see here that the BPD patients were higher than the other groups on athletic ability and impulsivity, which is not unexpected.
So our hypotheses were that consistent with prior work and mercial enhance concept of emotion regulation, that we will see that the BPD patients would show exaggerated effect of startle, during unpleasant social pictures, and they would show significantly slower habituation, the unpleasant pictures, we did a nice, multi model and a man over here looking at the groups and looking at some repeated measures.
And what did we find? Basically, you can see on the left side, that the BPD patients showed exaggerated amplitude of their startle blink response during the unpleasant pictures compared to the other two groups.
And they didn't differ from from the other groups on neutral or pleasant pictures. When we looked at this, because we had an interaction with trial block, and we looked at this over time, we saw that were the blue arrow is that the BPD patients actually show this effect primarily on the later part of the trials. So they actually go up in terms of their blink amplitude over time, after they're continuing to see these unpleasant pictures. And this was not seen for neutral or pleasant pictures.
But when we look at their self report, similar to the fMRI experiment that I told you about earlier, we see a mismatch.
So while they're startled blink response, which is linked to their amygdala is high. Their self report is that the unpleasant pictures aren't really that bad compared to the healthy controls.
So a dissociation again, between their physiology and their self report. This is similar to work I did a few years ago, using a really nice word list I got from gilhooly who did a directed forgetting paradigm.
So these were unpleasant, borderline-salient words like alone, suicidal, ugly, they viewed the words on the computer and had to think about the meaning for them personally. We saw exaggerated effect of startle during the unpleasant words in borderlines compared to healthy controls, but no differences for neutral words. And on the bottom graph, you see there that we saw this mismatch with their self report. While their startle response was bigger to the unpleasant words, they said that they weren't really that bad and thinking about them.
This work is similar and really is replicating some recent work done by limberg and hom in Germany, where they show that BPD patients show exaggerated startle, during scripts that have a theme of rejection and abandonment compared to just kind of general unpleasant scripts, which is very interesting. Speaking to this idea that this is a very que specific kind of deficit that we see in the BPD patients. Similarly, when when Limburg parses out her groups and looks at you might because you might well be thinking that this is related to PTSD.
Here's evidence showing us that really, it's in the borderline patients that have no PTSD that this abnormality, this exaggerated startle response, which is linked to the amygdala is observed during, in this case idiographic personalized scripts about unpleasant experiences compared to generally unpleasant, neutral or pleasant scripts.
We've began to sort of look at individual differences in terms of effect of startle, given some work by Abner premer in Germany showing that dissociative symptoms are related to this aspect of startle abnormality and borderline personality disorder.
And interestingly, what we see is that it's the borderline patients that have low dissociative experiences on the D s scale, that are showing this exaggerated effect of startle response, interestingly, and it's not the patients who are highly dissociated. So for the clinicians in the audience, I'm sure this makes a lot of sense.
So just to summarize what I've told you today, consistent with a core clinical feature of BPD these findings provide some objective, measured psychophysiological evidence from affective startle and amygdala have exaggerated emotional processing in borderline personality disorder.
These findings extend prior work by indicating that excessive affective startle and BPD is specific to unpleasant but not pleasant pictures. However, the excessive amygdala activation is observed for both unpleasant and pleasant pictures.
So I'm actually grappling with this as I'm trying to submit my afflictive startle data which doesn't quite replicate my amygdala findings, in contrast is psychophysiology. On self report measures BPD patients rated unpleasant pictures as being more pleasant and pleasant pictures as being more unpleasant compared to the healthy controls.
This is consistent with prior work done by Antonia new and others suggesting that BPD patients have trouble perceiving their own emotions, both the bad and the good ones.
And lastly, in support of the concept of specificity, the observed BPD related emotion processing abnormalities are not observed in schizotypal personality disorder. So I would like to conclude by saying Affleck of startle, and the underlying amygdala abnormalities that we see are consistent with Linehan's concept of emotion dysregulation, which is an inability to regulate emotional responses characterized by high sensitivity to emotional stimuli and unusually strong and long lasting reactions. And our findings suggest that effect of startle
This is the sales pitch may be a useful adjunct to self report for assessment of emotion processing dysregulation and treatment outcome.
And it's a promising potential biological endophenotype for emotion dysregulation.
Looking ahead, actually, the future came before the present yesterday because Maryann presented where I think this should go, which is really looking at biological predictors of treatment response using psychophysiology. And perhaps the amygdala centric approach of looking at the amygdala and habituation.
Thank you. I want to thank my collaborators too many of which are here, Marianne and Antonia and Mercedes and also some support always useful.