[00:00:01.610] - Wesley
You're listening to Journal Injuries, a podcast about philosophy and cognitive science, where researchers open up about the articles they publish. I'm Wesley Buckwalter. In this episode, lead author and Andrew Peterson talks about his paper Alive Inside, published in the Journal Bioethics. Andrew is an assistant professor of philosophy and a fellow, an Institute for Philosophy and Public Policy at George Mason University, a Greenwald Scholar and an affiliate researcher at the University of Pennsylvania Memory Center, known for his work on the ethical issues related to neurology and human consciousness.

[00:00:35.950] - Wesley
As we learn more and more about the brain, researchers are developing amazing neuroscientific methods that can help diagnose patients with traumatic brain injuries. But as these technologies develop, they also raise a number of important ethical questions, which are the topic of Andrews paper.

[00:00:55.680] - Andrew
Imagine that your loved one is in a car accident, heaven forbid. Right. And your loved one is rushed to the hospital. Your loved one is not responsive at the scene of the accident and not responsive when they get to the hospital, despite all the best efforts of the critical care neurologist that's there and there are critical lists there and remains unresponsive. Right. So when you say your loved one's name unresponsive, when you ask the loved one to raise her arm to command, she's unresponsive. Right. So just appears to be comatose, UN, arousable, unaware.

[00:01:37.870] - Andrew
Right. There are some pretty critical decisions that need to be made in that early period of time. Right. Do we want to continue with treatment, or is it the case that you want to withdraw care? That sort of awful decision. And families are often stuck there, and they're forced to make decisions that are really difficult with a posity of information. And clinicians are equally stuck because they want to give as much information as possible to families to be able to make the best decisions for their loved one.

[00:02:14.180] - Andrew
But it's hard to predict whether patients are going to recover after a severe brain injury. So that's the world that we live in.

[00:02:22.270] 
Right.

[00:02:22.860] - Andrew
But now, imagine a world where you could use a sophisticated neuroimaging scanner. You could slide your loved one into a scanner and determine early in the recovery process while that individual is still in the neurocritical care unit, whether that patient will recover for one and what that kind of recovery will look like. It turns out that that's the world that we're soon going to be living in. Clinicians in this area have always been sensitive to the ethical issues because they're dealing with them sort of on the front line, right.

[00:02:58.980] - Andrew
Through these life or death issues. But I think that people are in this area are becoming more sensitive to concerns about prognostication and the use of new imaging technologies to improve prognostication. You may wonder why a philosopher all of a sudden got interested in thinking about brain injury, and it's kind of serendipitous. So I did my PhD at the University of Western Ontario. I was supervised by both research ethicist, but also a neuroscientist. And it just so happened that the neuroscientist that I was working with was looking at issues of brain injury and the recovery of consciousness following brain injury and using really sophisticated neural imaging techniques to determine whether patients who had severe brain injury, we're going to recover from one or had preserved consciousness that was undetectable at the bedside.

[00:03:52.780] - Andrew
And it was actually like a really great sort of meeting of the minds, so to speak. Sometimes when you interact with scientists, they're very skeptical of having philosophers in the room, particularly philosophers that are interested in research ethics or in bioethics. But these neuroscientists, this lab was very receptive to participating in collaborating with philosophers because they realize that questions that they're struggling with in their lab were deep philosophical questions and had really profound philosophical implications. So that's sort of the Genesis of the relationship that came to a paper like this.

[00:04:34.140] - Andrew
And there's a variety of papers and a variety of teammates that I've had in thinking through these issues. So I want to make sure that I acknowledge that this is a paper that sort of is one stepping stone in that collaboration. The paper, though, itself, really was a reaction to a policy change that occurred in medicine in 2018. So various societies in the United States medical societies got together and produced a new clinical guideline called the Practice Guideline Update on disorders of consciousness. And these practice guidelines come out often.

[00:05:16.240] - Andrew
So it's just it's the growing pains of medicine. We do research. We figure out that there's better ways to treat patients. And then that kind of research goes through the pipeline to clinical practice and become standard of care. And the way that it becomes sort of standard of care is a political process here. You can see that it actually becomes standard of care when it's integrated through this Practice Guideline update. And this is not to say that it's like a purely political process. It's really predominantly an evidence based process because there's a lot of background work that goes into determining whether these new investigational techniques work in patients and then how they ought to be brought to the bedside.

[00:06:02.210] - Andrew
But this is what really motivated the paper. Right. And in The Practice Guideline Update, there are various recommendations to use neuroimaging to assess patients with disorders of consciousness and the particular applications of neuroimaging that are outlined in The Practice Guideline Update are kind of revolutionary. It's actually asking physicians, in particular cases, to use neuroimaging to detect something called covert consciousness. And that's really revolutionary in the practice of neurology for assessing patients with sphere brain injury. So the technique that was developed at the lab at the University of Western Ontario, Adriana Owens lab, the technique that everybody always refers to is called the mental imagery paradigm.

[00:06:53.080] - Andrew
So the way that this technique works is that you slide anybody into a scanner and you ask them to imagine one of two activities, playing tennis or imagine moving from room to room in your home. And it turns out that imagining these two activities preferentially activates different areas of the brain. Imagine playing tennis activates the supplementary motor area, whereas imaging moving from room to room in your home activates a network of brain areas that's associated with spatial navigation to the poster Parital cortex, the parahippocampal place area in the pre motor cortex.

[00:07:32.220] - Andrew
And these are spatially distinct brain areas. And so you ask a patient or any participant to imagine one of these activities for discrete and repeated 32nd interval. So you're in the scanner right now, I ask you, imagine playing tennis and continue to imagine playing tennis until I tell you to rest or imagine moving from room to room and one's home. All the different layout of the room where the furniture is, what the walls look like, so forth and so on. And keep doing that until I tell you to rest.

[00:08:07.820] - Andrew
And what researchers can do. What clinicians can do I use in the clinic is that you can decode from the neuro imaging data itself, whether the patient is volitionally modulating their brain to activity. So the reason why this is important is that it turns out that some patients with brain injury are able to do this even though they're not able to raise their arm to command. So the way that we would normally figure out whether a patient is aware after a severe brain injury is whether they can volitionally follow commands.

[00:08:41.640] - Andrew
Well, it turns out there's this new way with neuroimaging sort of peer into the black box of the brains of these patients to determine whether, just through imagining these these activities, whether they're responding to commands. And there's been a variety of studies that have used this technique, and it's on the order of about 15% to 20% of patients who appear entirely unresponsive at the bedside, diagnosed as being in the vegetative state, a state of wakefulness without awareness that those patients are actually covertly aware. We sometimes use the term covertly conscious.

[00:09:21.750] - Andrew
That's a pretty large amount of patients who we thought were completely unconscious, they're actually conscious, but they're just sort of trapped inside their bodies. The thing that's kind of remarkable about this technique, too, is that various labs have taken this technique and have used it to communicate with patients. So the way that you can communicate with this technique is to code the imagine activities with the answers yes or no. So you instruct a participant to imagine playing tennis if she wants to answer yes to a question, or imagine moving from room to room in your home if you want to answer no.

[00:10:04.910] - Andrew
And it turns out a variety of patients have who we thought were in a vegetative state. We're actually able to communicate with this technique and answer fairly sophisticated questions. So we had been thinking my co authors and I have been thinking about this issue for quite some time because this is the neuroscience lab that I was in was developing these techniques themselves. So we thought that this was a perfect time to sort of revisit some of the key ethical issues that people have struggled with. Are the use of these neuroimaging techniques going to facilitate false hope among caregivers?

[00:10:41.440] - Andrew
What about the quality of life of these patients? Is it actually going to perpetuate harm, or is there any benefit to using these techniques for these patients? And finally, is it worth the cost? It's really expensive to use these these techniques. So we use this as an opportunity to really sort of revisit those questions in a way that sort of tackled that the policy change that happened just recently. But to use it as a way to think more deeply about the ethical considerations that come from this policy change.

[00:11:18.420] - Andrew
This is one of those things where when I was a graduate student working on this, I have sort of naive view that if you detect over consciousness in these patients, it's like we've done it. That's the goal. Right. But when you disclose that kind of information to patients, families, it's kind of the kind of response that they've they gave was so what do we do now? And it turns out that there's not a lot that you can do at least four chronic patients. Patients. When I say chronic patients, I mean, patients that are a year out after their injury or more in some of the patients that we assess, they were five to ten years.

[00:11:59.360] - Andrew
They had been in a vegetative state. So clearly, families are very committed to these patients. They want to make sure that they stand by them. But, yeah. I mean, there's kind of response you get from them is so okay. So what's the next step? What's the kind of therapy you've detected there is covert consciousness. Now do something about it, bring my loved one back to me. That's what people really want. But that does shed light on the really interesting application these techniques not in chronic patients, but in what we would call acutely comatose patients.

[00:12:36.730] - Andrew
The acute population is where there's real promise for this technology. And those are patients that are within 72 hours or a week of their brain entry. So they're really, really sick patients. They're typically patients who appear comatose at the bedside. They're in the ICU. And those are when some of the real critical decisions are made about continuation of treatment or withdraw of treatment. And again, as I started off this conversation, families are sort of stuck, and clinicians are stuck with a posity of information and uncertain information at those junctures.

[00:13:17.310] - Andrew
And if there's any decision that we would ever want the most certainty with, it's like the decision whether it'll live or die, we want to have as much certainty as possible. So it turns out that you can use these techniques, though, not merely just to determine whether a patient is covertly conscious, but you can use them for improvement of prognostication to give better prognostic accuracy for patients with severe brain injury. Are these patients going to recover? And what is that recovery going to look like? And the handful of labs that are seriously working on this in the United States and throughout the world are really focusing their energy on that now.

[00:14:01.020] - Andrew
And it turns out that from a policy standpoint, too, it's a good place to focus your energy, because if you can make the serious these critical decisions early on, then it can affirm to you that your investment of time and money and caring for these patients down the road is actually worth it. Or worth it for the reasons that caregivers and patients specify. Right. Because there's a variety of reasons as to why caregivers might want to continue care, but at least they have that information at hand so that they can actually make informed decisions as opposed to going through life, caring for their loved one, and always being uncertain.

[00:14:42.040] - Andrew
We they're ever going to recover, or whether they're conscious, whether they can hear their voice, whether they can feel the sort of touch of their hand when they visit them in the hospital. One really serious worry that's come up with this kind of work is how family caregivers understand neuroimaging results when in their disclosed. So one the possibility of even offering neuroimaging as a way to assess patients to determine whether they may be covertly conscious, but then Additionally, how you disclose that information to them. So it's not one to either raise something called therapeutic misconception, which is the idea that like what's going on in the investigational space.

[00:15:31.160] - Andrew
The research space is actually going to confirm any kind of therapeutic benefit to the patient. We don't know if this really works yet. We want to make sure that it really works in the research setting before the clinicians can make claims about it, actually confirming improving diagnostic accuracy or prognostic accuracy. So that's one concern, but then the other concern is just generally raising false hopes. Right. So you get some neuroimaging information back. The information is it maybe may be indicative of a patient having preserved cognition, or maybe sort of marginal.

[00:16:03.940] - Andrew
In any case, you can imagine that a family who perhaps distraught is trying to process all this information. They may sort of latch on to that and sort of develop false hopes about the possibility of recovery. Now, it turns out, though, that these kinds of concerns, serious ethical concerns about therapies and misconception and false hope are rather speculative. Bioethicists have worried that disclosing this kind of information to patients families will cause false hope or cause therapy. Misconception lead to it. But it's never been tested empirically until recently.

[00:16:44.790] - Andrew
We just finished up a qualitative interview study of character Rivers of patients with disorders of consciousness who went through the neuroimaging research program at the University of Western Ontario, the one that I just described. And they went through a gamut of neuroimaging techniques. And what we want to assess with this, we did an interview with these caregivers before the patient underwent the neuroimaging tasks, and then an interview after they received the neuroimaging results. And what we want to assess was whether they actually understood the results and whether that led to false hope.

[00:17:23.620] - Andrew
First, it didn't read to false hope or therapeutic misconception in the way that bioethicists think that it would. In fact, all the families, the caregivers that went through the study had a very, very sophisticated understanding of the study itself. And the results irrespective of the kinds of results that they received, whether it was null results or results that were consistent with covert consciousness. However, the folks that did receive evidence of covert conscious. So my intuition was like, oh, you're going to receive evidence of covert consciousness.

[00:17:59.600] - Andrew
This is gonna be a great thing. This is going to be sort of life changing for you. Turns out, it wasn't getting evidence of covert consciousness is really complicated to process, and it's really complicated to share with other family members who are once removed from that disclosure process. So, for instance, a lot of family caregivers who received evidence of covert consciousness sort of latched on to certain terms that the research team used when they were disclosing the evidence, the results, such as brain activity or brain activation.

[00:18:33.380] - Andrew
And they became sort of bewitched by these particular terms, and all the other sort of pertinent scientific or clinical facts sort of faded to the background. And when they shared that information with other caregivers with other people in the caregiving network, but who are once removed from the disclosure process, you got this sort of telephone effect. So they would they would share that information with the other family members, and then the other family members would think to themselves, oh, my gosh, that must mean that John is waking up tomorrow or, oh, my gosh, that means that Jane is waking up tomorrow.

[00:19:10.050] - Andrew
So it's important to note that the people who actually had the information disclosed to them, who are counseled by the research team themselves, they understood they didn't show any evidence of false hope. They didn't understand show any evidence of therapeutic misconception. It takes a village in these cases to care for a patient. And sharing that kind of information with other individuals did lead to this complexity in the way that people understand this notion of covert consciousness. The other thing that was really interesting in that scenario in this study, too, is that when we disclose null results to some caregivers null results, meaning that there was no neuroimaging evidence of an effect in these kind of scenarios, we're not able to say that the patient is actually unconscious.

[00:20:00.300] - Andrew
The patient may have fallen asleep during the neuroimaging task. Patient may have auditory impairments secondary to brain injury that make it impossible for them to actually go through with the neuroimaging task. So there are various confounds that may bear on a patient's capacity to perform the task. So we always go into the disclosure process, framing it as uninformed results if there's no indication of covert consciousness. But some caregivers who received that information are actually resistant to the information. And instead of being accepting of the information, they turned around and they started challenging the validity of the neuroimaging test themselves, claiming, for instance, well, it's just research, right.

[00:20:52.080] - Andrew
Or I'm surprised that you guys didn't do X, Y, and Z, because I do those kinds of sensory stimulation techniques at home, and those turn out to be much more sensitive. And I actually see a significant amount of reaction from the patient at home. So there's a really interesting nuance here to the psychology of hearing information that sort of conflicts with your worldview about a patient. Right. And again, we went into the study just to determine whether there was an issue of false hope or therapeutic misconception.

[00:21:27.680] - Andrew
What we found with a study, though, is that during this disclosure process, the story is so much more complex and really turns on the sort of psychology of caregivers, how they understand terms like consciousness, what their goals of care are, what their sort of deep seated views are about the patient to begin with, which are sort of they're all couched in, like, this long relationship that they've had with the patient up until the brain injury and after brain injury, as they've been caring for them. There's a really interesting sort of ethical issue that's embedded in what kind of evidence we think is sufficient to ascribe consciousness to these patients.

[00:22:07.200] - Andrew
There are a lot of people who think that the evidence is insufficient to ascribe consciousness to these patients. But it seems to me that there's a lot at stake if we don't ascribe consciousness to the patient, but they are conscious. Right. We have a false negative that might imply that we would prematurely pull the plug on some of these patients or treat them in a way that isn't commensurate with them actually being conscious, whether it's through the application of pain medications or something like that. But on the other hand, if you set the evidentiary standard lower, you might get a lot of false positives in that case.

[00:22:46.890] - Andrew
And in that case, you're going to have a lot of patients who aren't conscious at all that we're detecting with neuroimaging that they are they may be conscious. Then you might prolong the lives of these patients and impact their dignity when family members or expressing their advanced directed that they actually would want care to be withdrawn. You may raise false hopes in these individuals. It may also lead to serious cost considerations, too, because it's very expensive to care for one of these patients. Years, I started off this story by talking about the practice guideline update and how revolutionary the Practice Guideline update is.

[00:23:32.770] - Andrew
But there are some philosophical puzzles that remain about the Practice Guideline update. They're really important for philosophers, for bioethics, for health policy experts to weigh in on. And they also illuminate some really interesting questions about how evidence based recommendations sort of meet the road of clinical practice. So as I mentioned, this practice guideline is incredibly rigorous. All the recommendations are evidence based, and they want the folks who put it together went through an exceptionally rigorous process to determine what the evidence base is for particular recommendation, how strong that evidence base is so forth and so on.

[00:24:15.180] - Andrew
But for some of the recommendations that don't have as strong of evidence base, there are particular caveats in the recommendation that instruct individual physicians to weigh the harms and benefits of applying this recommendation. And practice neuroimaging, for instance, or multidisciplinary neurorehabilitation, for instance. Those are some of the recommendations. It asks individual physicians to weigh the harms and benefits of that recommendation, the feasibility of applying that recommendation in practice for a particular patient, and the potential cost relative to benefit for a particular patient. And throughout the recommendations, there's no description as to how individual physicians ought to sort of grapple with those concepts.

[00:25:07.200] - Andrew
It's not actually fleshed out in the document itself. So when an individual physician in the Midwest has a brain injury patient, it's just gone in a car accident, and it's very keen to sort of follow the evidence based recommendations to the Tea. But then they get to these caveats about how to sort of weigh benefits and risks, like How's that individual physician supposed to do that. How much is it cost? What's up? How much is it cost? Right. I think it's probably going to vary. So I think the bigger issue is this sort of auxiliary costs that are associated with it is making sure that you actually have a neuro imaging unit that's like that at the particular hospital in the Midwest.

[00:25:51.990] - Andrew
And, Wayne, the amount of time that it takes to do one of those communication sessions versus the use of the neuro imaging unit to assess other patients that may also need right. So there's sort of trade offs that are done. There are serious efforts to translate these techniques into something that's cheaper, and it's more portable. So all these techniques have been developed with fMRI, but most of them are trying to be translated in to E. So that's like the real push right now. But the concern from a policy angle is that okay.

[00:26:30.240] - Andrew
Well, we have these evidence based recommendations now. But given these sort of normative caveats and these normative instructions within certain recommendations, there's the possibility that the evidence based recommendations could be applied unevenly across the United States because you're going to have individual physicians making sort of ad hoc decisions as to what is beneficial to a patient, what is harmful to a patient, what is feasible to a patient, whether the costs outweigh the benefits for a particular patient. And that's, I guess, from a Philosopher's brain, is that when you have rules, you should follow the rules.

[00:27:04.490] - Andrew
And it seems strange to think that there's flexibility to the rules. But on the other hand, when you think about it from a medical standpoint, this is really where you get to the Gray area that sort of edges the margins of evidencebased medicine. And you start to see that medicine is just as much of an art as it is an evidencebased practice. This is a fascinating feature, thinking through the problem of how to apply these practice guidelines in practice in a consistent way. It's a fascinating exercise to think about how recommendations in medicine get to the point where the rubber meets the road and how to do that in a way that preserves maximum flexibility for individual physicians that are struggling with, you know, patients that are going to come with all sorts of different, perhaps comorbidities, or all sorts of different patient histories.

[00:27:59.570] - Andrew
But then also trying to apply these sort of generalizable rules about how to care for these patients to individual patients. In some senses, it seems to sort of map on to the same concerns that we have in philosophy about having sort of generalized moral principles, but then also being able to take those generalized moral principles and apply them to particular cases. But I think more generally, if you sort of abstract a little bit and you think about the relationship between sort of philosophy and neuroscience and ethics, I think that people are starting to appreciate that there's a great synergy between all of them.

[00:28:37.030] - Andrew
And you see this through initiatives like the Neuroethics Arm of the Brain Initiative, for instance, Brain Initiative, developed by the Obama administration, which is intended to unlock the mysteries of the human brain and various pathologies of the human brain. But then I think that the NIH is very sensitive to the ethical issues that come up because the brain is one of those critical organs that makes us us. And I think that there's recognition that philosophers who have been tackling these kinds of questions about the sort of intrinsic properties of being human, that philosophers can bring fantastic insights to the scientific process here about how guiding the science of what questions are important to us then.

[00:29:27.130] - Andrew
Moreover, it's sort of how that information can be used to enhance human flourishing generally. That's it.

[00:29:40.360] - Speaker 1
For today's episode, funding and part was provided by the Institute for Philosophy and Public Policy at George Mason University. Visit our website at Journal entries fireside FM for more information about Andrew Peterson, his work, and some of the resources mentioned in this episode.