The brain is, in the words of Emily Dickinson, wider than the sky. Since the discovery of the brain in 17th century BC, man has been developing new tools to assess the brain. On today’s podcast, Dr. Diane Hamilton brings on Dr. James Giordano to talk about the neuroethical aspect of brain science, digging deep into the brain science of morality and ethics and the ethical, legal, and social issues that arise in and from neuroscience and its varied applications in biomedicine, public life, and daily occupational pursuits. Dr. Giordano is a full Professor of Neurology and Biochemistry, Chief of the Neuroethics Program, and Co-director of the program in Brain Science and Global Law and Policy at Georgetown University Medical Center, Washington, DC. He has over 300 publications in brain science, ethics and biosecurity.
I’m glad you joined us because we have Dr. James Giordano here. He is a full Professor of Neurology and Biochemistry, the Chief of the Neuroethics Program and Co-director of the program in Brain Science and Global Law and Policy at Georgetown University Medical Center. This guy is a genius and his knowledge about the brain is unbelievable. I’m excited to have him on the show. We’re going to get into many fascinating topics about the brain neuroethics and biochemistry.
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Brain Science: Accessing The Brain And Its Functions Ethically With Dr. James Giordano
I’m here with Dr. James Giordano, who is a full Professor of Neurology and Biochemistry, Chief of the Neuroethics Program, and Co-director of the program in Brain Science and Global Law and Policy at Georgetown University Medical Center, Washington, DC. As well, he’s a senior bioethicist at Defense Medical Ethics Center in Bethesda. He’s a senior fellow of the US Naval War College and distinguished visiting professor at both Creighton University and Coburg University of Applied Sciences in Coburg, Germany. You’ve done so much work, Dr. Giordano, with 300 publications in brain science, ethics and biosecurity. That’s impressive. Welcome to the show.
Thank you. It’s a pleasure to be here.
A few peer-reviewed publications I have, I can’t imagine 300 or more than that. Brain science is intense stuff. Did you grow up to think you wanted to go into brain science? I need a little background on you to see how you got into this.
I like to joke. I said I want to get into the Plumbers Union and they wouldn’t take me, but there’s no humor there. That’s a hard union to get into. I have some relatives of mine who are plumbers. Keeping the plumbing thing going, my dad was a nautical engineer and he worked designing submarines. He worked for an American electric boat and for a number of other freelance companies. Three hundred publications, I’m an old guy. I grew up in the 1960s and that was an age of exploration and adventure. We were going out of the space for the first time. I remember those old Mercury rocket liftoffs and watching them on TV.
We’re also going to the depths of the ocean with the Trieste. That was the bathyscaphe and bathysphere that was plumbing the depths of the ocean. I was about 5 or 6 years old or maybe a little older, about seven and my dad took me to see a movie called Fantastic Voyage with Stephen Boyd and Raquel Welch. I thought that it was the most amazing thing I’d ever seen. My dad was a submarine designer. He would always have model submarines in the house but this idea of while the brain and human body. I remember I came out of that movie and I said to my dad, “That’s what I want to do when I grow up.” I remember he chuckled and he went like, “Yeah.” Things worked out advantageously and that’s what I do.
I can remember sitting and watching the moon landing and all the things that happened in the ‘60s. It was an exciting thing when you’d get a movie like that or something that made you think in a different way. I used to even like the old Star Trek with the brains in the jars. I bet you love that one. I’ve often said to my husband when we were watching The Big Bang Theory. I said, “I’d have to be Amy Farrah Fowler because I’m interested in the brain of the characters on that show.” It’s fascinating how little we know, and yet we think we know a lot. How much do we know do you think of what there is to know about the brain?
I like the quote that the brain is, in the words of Emily Dickinson’s paraphrased, wider than the sky. In many ways, I think that’s quite true. What’s happening is we’re developing new tools to be able to assess the brain. From those, we’re getting newly identified targets to be able to affect the brain in a variety of different ways that span all the way from the subcellular right up to the socially interactive. We can take a look at our understanding of the brain on three fundamental levels. Do we understand the structure? We’re getting a better picture of that with some of the tools and techniques we have. Imaging techniques, cellular techniques, genetic techniques, looking at the interaction between genes and physical expression of structure and function. We understand some of the larger physiological concepts of the brain, how the brain interacts with the body, and how the brain controls our physiological systems in a variety of ways in response to our environments.
There is what’s sometimes referred to as the hard problem or the hard question of brain sciences, which quite simply put and this is to paraphrase the cognitive scientist and philosopher David Chalmers. We simply don’t know how the great stuff of consciousness of mind, the feeling of self, arises from the gray stuff that’s in your head. We simply do not know how the mind occurs in the brain. We have some good theories, but they’re just theories and some were a little bit better baked than the others, but that’s still a pervasive question. In some ways, the larger question is, do we need to know that? Can we continue to proceed by getting patterns of correlations between structure and function and use that in a variety of different ways in medicine, public life and a host of other applications?
It’s an interesting area of study. I looked a little bit into it when I wrote my dissertation on emotional intelligence. Looking at the impact of different aspects of stories like Phineas Gage, who got the steel bar in the front of his brain and what he was able to redevelop and different structures of what’s impacted. When I was studying curiosity, I looked at dopamine and some of those things, but my level of understanding compared to what you study is minimal. For our readers who don’t understand this as well, what is the big thing that you’re working on in brain science? What are researchers looking at that they’re struggling with and how far are they along in the process?
There are two questions there. One is what I’m working on, which represents a tiny little grain of sand on the vast Sahara of this discipline of yours. The other is what are the foci and areas of the field that represent key aspects of development that are going to be scientific biomedically and perhaps even socially relevant. Let me take the one that’s easier, which is what I am doing in my own backyard. These days with COVID, I’m working from home and there’s been a moratorium on some of the research. The nature of the research primarily is on how nodes and networks of the brain dynamically interact to create these patterns of cognitions, emotions and behaviors. I’m interested in the way that those nodes and networks react and respond to engage what we consider to be morally relevant decisions and actions.
Scanning and accessing the brain opens a virtual Pandora's Box of both goodies and goblins. Click To TweetOne of the other areas that I’ve studied for a number of years is the way the brain responds to and processes various types of pain and pleasure and those are not going to relate it. A lot of the things that we feel are good for us, good to us, feel good and provide us with some reward, we engage in. Often, those are the things that we define as good and those are the things we seek. That goes along with our moral cognition and those things that we find to be punitive, problematic, distressing, painful and uncomfortable. Those too are the things we codify as individuals and social groups, perhaps even as large-scale cultures to say these are the things that represent punishment and negative reinforcement. Things to avoid for both self and others. Everything forms together.
The basis of my work is looking at the way new tools and methods in the brain sciences can be used and in some cases, misused to be able to appropriate a deeper understanding and access to the brain space and its functions. That’s where the neuroethical aspect comes into it. Looking at both the brain science of morality and ethics and the ethical, legal and social issues that arise in and from neuroscience and its varied applications in biomedicine, public life and daily occupational pursuits. Also, what some people have termed the dark side, which is there’s a lot of power in science and technology, and brain science and technology is no different. This could have various applications in national security, intelligence and defense initiatives. That’s my work. Right now, the field is focusing on developing over newer, more granular, precise and sophisticated tools and methods to be able to both assess the brain, harnessing a variety of different techniques that go from the very subcellular all the way up to the large systemic. Also, being able to access the brain.
That’s where the field is looking to make inroads, the ability to utilize a variety of different techniques and tools. Some are donable and doffable that you can wear and take off. Some are available directly to the consumer. Others that are available clinically. Things that are implantable can then be scaled in such a way that need not have surgical implantation to be able to create a vast array of electrical and electromagnetic networks within the brain that can be sensed and/or contacted remotely. We’re right on the doorstep of being able to scan and access the brain. By scanning and accessing the brain, we then have access to and the capability to affect those functions of the brain, which are mind cognition, emotion, behavior, sense of self and personality. That opens a virtual Pandora’s Box of both goodies and goblins.
I’ve taught a lot of ethics courses and one of the fun things about teaching ethics is how subjective it is. You can get people all rolled up in class. You get both sides of a subject. I’m picturing this Neo from The Matrix with a USB port on our head. Is that going to be how it’s going to be where we can learn something without the journey? Is there a loss of the journey that we should limit?
There are some philosophers, ethicists, and scientists internationally the two that I’ve referred to here, Thomas Metzinger, the German cognitive scientist and philosopher, and others who’ve pointed to our increased use of technology. I just don’t mean brain tech here. I also mean things like artificial intelligence, decision technology, and the ubiquity of information that’s provided to us over computers that we have either on our desks or in our hands and increasingly everywhere on our ear. We all have Siri and Alexa. The ubiquity and the convenience of those things put information at our fingertips, in some cases, at the tip of our tongue. Increasingly, what we’re moving towards is the possibility of a little behave to generate that through thought. That’s not difficult to do. The idea of brain-computer or brain-machine interfacing is capable of doing a number of things that allow us to engage in control machinery, inclusive of computational machinery.
This isn’t create a new world. This is bold new brain science, but I think that the larger issue there is where we’re going with this. What does this mean? What will happen as a consequence of doing this? The thing that becomes important for readers even consumers to understand is that we are moving ever more towards brain science that’s accessible. Brain science in your backyard, direct to consumer markets for brain science and neurotechnology, and becoming more comfortable and capable with the use of advanced techniques and technologies in biomedicine. Even in biomedicine, if we think of something like preventive medicine, there’s a thin fuzzy line between what represents a preventive treatment or intervention and what could represent optimization enablement or enhancement.
The question then becomes, “What are we gaining when we gain this? What are we losing when we lose this?” It gets back to Metzinger’s issue, are we creating digital dementia or are we simply shifting the way we use, acquire, gain information and the way we think? The probable answer is the latter. We can look at some of the work of the philosopher in cognitive scientist, Merlin Donald. He has done a wonderful leadership. He charted out the epoch of human cognitive development. We’re at the point now where we’re increasingly relying on things technical. What we’re doing is we’re using our tools as we have always done, but with an increased level of sophistication, rapidity, expansiveness, and complexity to gain information, to synthesize, and assimilate information. Also, to employ that information to build other tools to engage other methods.
What we’re looking at is an epistemological shift. In other words, what we know, how we know it, and the way we use the things we know are changing as a consequence of the tools we have at hand, which has always been the case. We started out with sticks and clubs and worked our way up to more sophisticated machine tools. We went from little carved out logs that we thought would float down the river to steamships, submarines and nuclear-powered vessels. The pace is accelerating and with that, the sophistication and capability. The question then becomes, what is gained and what is lost? I think we’ll be gaining a lot but the question is, are we ready for those gains socially, civically, culturally and economically? I don’t know the answer to that question.
I’ve talked to different people. Albert Bandura was on my show, which was amazing to talk to him. You talk to everybody in psychology, sociology and different realms of where we’re headed. It made me interested in my research in perception, which I’ve had Beau Lotto and others on the show. We talk about the way we get involved right now, confirmation bias is a real hot topic. Do you deal with mapping the brain for things like that? We’ve talked about before how you look for pleasure, pain, different things, sometimes light up a screen. Can you look for all different behaviors and reactions from that type of thing or is it something you can’t map?
You can at least in part. I think what it’s important is to understand what the metrics are for that. In other words, to know what it is you’re looking at and what you’re looking for. Some of the advances in correlative neuroimaging, where we’re not taking a static picture of the brain, but we’re taking a look at relative brain activity. We’re mapping that on top of node network activity, which is sometimes referred to as tractography. We’re doing something further. We’re creating a larger scale map across a range of scales and that’s called connectomics. We’re able to visualize what nodes and networks are interacting, what time and directional period and relative frames of temporal windows within the brain. That helps us to then understand what parts and areas of the brain are connecting and what ways when we’re processing different types of information.
The goal here is to create a large enough repository of data to be able to provide inter-individual comparisons and metrics, as well as individual to group and group to individual metrics. In that way, we create an atlas of structural-functional brain correlations. It’s a huge undertaking but the key to that is big data and artificial intelligence and decision technologies. We’re working our way into the proverbial atrium of that possibility. We’ll see that for the next coming years to be able to map the brain more effectively. It’s then the question of what cognitions, emotions and behaviors we’re looking to effectively map?
In my technology courses, we talk about ethics and technology. We talk about, do we use CRISPR, do we use these different ways to change what we have genetically and what are the ramifications of those down the road. As you’re talking about mapping, in my mind, I’m thinking of interviewing people like Jürgen Schmidhuber and people who have dealt with AI. How closely are they making these artificial intelligence computers or whatever you want to call them to mimic the brain? Can you make it to be close to how our brain works or is it a different mechanism of action of how they work?
It’s a bit of both. The brain functions as a computational system. The brain does this function in computation across time and space stream. It plots what you know to what you’re encountering and what that then means predictably for the present. It also does that spatially what’s inside and what’s outside. The function of the brain is some form of computation, but the computer does not necessarily work as a brain nor do we want it to. One of the various forms of artificial intelligence is to have neural-like networks, but then also to perform in ways that are not necessarily neural. In other words, to do more than a neural network could do to utilize a vast array of inputs and outputs and to try to do so in such a way that creates viable information transfer in a scale that may not be capable of use by the human brain or any living brain.
That’s not the real limitation. The limitation that we’re looking to overcome is, can you then yoke those systems? In other words, can we create reciprocally cooperative systems? Machine systems that then in some way, compensate and/or synergize for the capabilities or weaknesses of the human user and vice versa. You create a cooperative system, a human machine interface, utilizing the human brain and/or an animal brain and some form of machine technology that has some viability to develop some form of artificial intelligence and decision technology synthesis. You create a human-machine system dyad where the capabilities of the system are synergistic. What you get is reciprocal compensation for the inadequacies, gaps and weaknesses of the system. Then you’ve got something because what you’re able to do is develop machine systems that learn directly, not only from a human user but from its experience with humans, and that takes AI in a distinct trajectory and direction.
Do you worry about that direction? Elon Musk and others have warned that sometimes that could be problematic.
Elon Musk is a talented guy. He’s a great entrepreneur. I pushed back a little bit on some of these false representations of a singularity or the threat of the rise of the machines. What we’re seeing is the ubiquity of information and information technology and the need to be able to keep up with that by harnessing that technology in a variety of ways from the simple to the complex. What we’re seeing more than anything else is an interreliance and interrelation between humans and technology. Particularly, artificial intelligent technology and what constitutes artificiality and reciprocity in that form of intellect. The issue here, more than anything else that I’m aware of, is threefold. Number one, if we’re going to create AI systems, do we want to do that with the human in the loop or on the loop and make it an autonomous system?
If it is an autonomous system, then will it have stake and shareholder values that it’s incorporated and will continue to persist with those values so that it will be capabilize and complementary to human activity? The third is, will we also put certain breaks on that system? As it begins to develop on its own, in other words, what’s called autopoietically. It begins to make itself and utilizes the web as its viable system. In other words, creates information as to its own platform. It doesn’t necessarily need a device, but rather utilizes these devices as portals. We then have some modicum of control to be able to maintain insight to what the system is doing, thinking and saying. Will it develop more knowledge and capability than we do and you then get what’s called reverse builders’ bias or a reverse Jehovah complex?
In other words, the system essentially becomes its own creator and leaves us out of the loop. Those are some real scenarios. Those are fairly realistic. We’re doing a lot of work. We started a Springer journal, which is called Artificial Intelligence and Ethics. It’s a great journal and it’s brand new. I have the pleasure and honor of subheading the area of biotechnology, biosecurity and ethics. It is provocative, in some cases, contentious area because the question is, what ethics do we utilize? What ethics will the system utilize and how to create the system? When you deal with your students, as I deal with mine, and even in larger forums, this technology is global. This is going on in an international level.
How do you get everybody to agree?
Different nations have different cultures, needs, values and ethics. What ethics do you incorporate, or what ethical flexibility do you incorporate to be able to make that genuine, authentic and meaningful?
What do you mean specifically by biosecurity?
What we know, how we know it, and the way we use the things we know are changing as a consequence of the tools we have at hand. Click To TweetThink of the COVID crisis. We’re still in the midst of that. There’s nothing that I’ve seen or no information that I’ve been able to have access to on a variety of levels that would suggest that this is a man-made virus. Is it possible that this was released inadvertently from a laboratory? We’ll leave all that to speculation. I think what COVID demonstrated is that societies globally are not prepared or readily responsive to deal with a biological threat. When we’re dealing with burdens, risks and threats to biological stability, individual and public health, that whole area of being able to maintain the stance of preparedness, readiness and response, is called biosecurity. There are biosecurity issues that go along with big data and AI.
Are you dealing with any blockchain ways of keeping things safe in what you’re working on? I’ve had a lot of people on the show that have dealt with blockchain to keep track of education systems and all these different things that you don’t think about. Does that tie into anything you deal with?
It does a bit. The whole blockchain system and the blockchain annex are a little bit out of my wheelhouse, but I’m fortunate to work with some real experts in the field. I rely upon their expertise because we’re using more of these blockchain type or direct blockchain mechanisms as support and engagement processes, to which we can articulate the science and technology in a variety of different applications.
As we learn more about this and the brain, we were talking about trying to come up with a code of ethics that everybody would agree on and that type of thing. Are we going to become more alike or more different from all that we learn?
The esteemed German scientist and cognitive scientist, Ernst Pöppel, said that what neurocognitive science has provided us a window to is our anthropological similarities and as well as our anthropological differences. Let me take and ground that to a deeper reality for the readers. What brains have in common are their differences. There’s an adage in neuroscience. It says neurons that fire together, wire together. The pattern of firing is dependent upon your experience, which means that James Giordano’s microstructure and microfunction of my brain in many ways might be quite different than Dr. Diane Hamilton. The reason is that different experiences have allowed different nodes and networks to become differentially active fortified or de-fortified. The devils and the deities live the details of the uniquity of individual brains.
Brains have a lot of things in common and those brains exist in bodies, and those bodies exist in ecologies. My hope is that getting a deeper knowledge of the way brain science can inform cognitive sciences, psychology, sociology, political science, anthropology, we’ll have a deeper insight into what makes us tick on a variety of levels, from the cellular to the social. That will help to inform human dynamic relationships and interactions once again, on a range of scales from the interpersonal all the way to the interpolitical. It’s optimistic. I don’t think it’s pollyannaish, but I think that there are a number of initiatives underway that recognize that neuroscience can be used for a number of things, even on the military side of the house. We look at national security, intelligence and defense agendas. A big component of the harnessing of neurocognitive sciences is to gain a better understanding of what are the triggers, vulnerabilities, and volatilities for violence so as to be able to de-escalate that through better human diplomatic and relational interactions on a host of scales, to be able to avoid conflict rather than promote it.
As you mentioned that, it makes me wonder if you’ve studied the brains or the situations behind some of the behaviors of some of these violent people, maybe the Ted Bundy’s of the world. Do you look into famous brains? Is that part of any of your research?
Not directly, but indirectly. Let me explain what I mean by that. I have the pleasure of working with an esteemed colleague of mine, whose name is Dr. Karen Herrera-Ferra. She was formerly my postdoc. She’s now running the Neuroethics Society in Mexico. Her focus is recurrent violent behavior, whether that occurs in a domestic, social or criminal scenario and even on a larger scale. We’re taking a look at repeated violence as a consequence of escalation to terrorism or war. What we’re studying is what that might mean. Are there actual patterns of neurological structure and perhaps neurocognitive function that might A) predispose individuals towards that escalation to recurrent violence, B) propagate that current violence? Are there also possible ways that might be mitigated and prevented?
This gets sticky because you’re beginning to talk about things like neuro correctives and this opens not only a Pandora’s Box but a can of worms and saying, “Should we use the brain sciences in those ways as to prevent and/or de-escalate or mitigate violence?” That’s a thin line between what is mitigation and manipulation and then you get into this whole minority report idea. This treads a thin wire and it requires a lot of discourse and study. We have to be careful about what defines use versus misuse versus abuse.
One of the other areas of the brain that I find the most interesting that I wish I understood more was sleep. Do you deal in sleep at all and the importance of it or why we even have it?
It’s interesting though because some of the newer neuroscientific studies of sleep have demonstrated that it’s far more effective in being able to consolidate certain brain functions. We can improve sleep efficiency in a variety of low-tech and high-tech ways to be able to preserve neurocognitive functions as a consequence of good sleep hygiene. I worked with a colleague of mine in Europe. His name is Professor Niko Kohls. His area of expertise is health promotions. One of the things he’s interested in is how we can harness both low-tech and high-tech in those ways that afford maximum benefit for individuals and communities. One of the ways we could do this is increased sleep hygiene, ensuring that individuals working back into the clock and clock shifted are not becoming circadian desynchronized. As a consequence of that, what things could we perhaps do to ensure their public occupational and even avocational safety?
All of these things merged together nicely within a health promotions model. The question is, how amenable will the public be to employing a variety of low and high-tech means? Even if we think, “All these things are great,” the next question is, will we have the funding and support for the continuity of research, even if when things don’t go the way we planned and will we have the continuity of care? Not only if when things don’t go the way we plan, but even if when things do go the way we plan. What that leads to is will we simply have the level of economic and social support necessary to translate the brain sciences and cognitive sciences into a usable public health tool. That’s an ongoing discourse.
There are a lot of discussions that don’t necessarily get resolved. I had the CEO of EyeJust, who creates a screen to block the blue light. She was talking about circadian. Have you studied the impact that computers, lighting, and everything’s had on the brain?
We have. Some studies that we did with Professor Kohls and another colleague of ours Professor Dr. Herbert Kitschelt out of the Munich Institute of Technology and Technical University Munich, looked at various wavelengths of light and how they affect not only circadian rhythm but also various patterns of neurological function, cognitive expression, and cognitive receptivity. What we understand is that we are circadian and trained animals. We do have a pattern of circadian rhythmicity that is modulated by certain systems of the brain essentially the secondary optical tract. What that then does is it regulates the production and release of a neurochemical called melatonin, but it also regulates the release of a number of other brain chemicals that work in concert.
We’re now beginning to understand that a lot of the synthetic light that we create has an effect because of the relative sensitivities of our retinas and also our neurological system to these various frequencies and bandwidth of light that may not necessarily exist or exist in a very different fashion in our natural environment, but in the constructed environment. We’ve been less attentive to some of these, but the more we know, the more we can go forward in such a way that is informed, informed in such a way that is beneficial to health promotions and public health.
It’s interesting to look at the research on that. With people I interview for different aspects of business research, the impact of dopamine and sometimes serotonin, but mostly you hear a lot about dopamine. With my research in curiosity, I found studies that said it helps improve your dopamine levels. You also get these experts on the show that say that your brain is where you have all these dopamine reactions, but then you have people who will say your stomach is more important than your brain when it comes to things like the feel-good types of having your brain have optimal results. Is it true that it’s more important that your stomach is in line for your brain to work properly? Am I hearing that incorrectly?
You’re hearing that correctly. Serotonin was originally called enteramine because it was first and localizing the gut. What we understand is that the gut in humans, certainly in primates and other animals is richly innervated. It has a dense neurological network. This neurological network contributes not only to our autonomic function, things we don’t think about, but this thing provides for us what the neuroscientist, Antonio Damasio brilliantly refers to as the feeling of what happens. We feel what’s happening inside of us. We interpret that in particular ways based upon our prior experiences, our erudition and our expectation. If my stomach is rumbling, I get a feeling for that. Even some of the colloquialism, I get a gut feeling. We recognize that there are particular reactions that are mediated by branches of the enteric nervous system that engage parasympathetic and sympathetic tone, that feedback to our brain that we interpret in certain ways.
What other functions might be subserved by these interactions? We have come to recognize that the ongoing tone that the gut-brain interaction can be important for the mediation and stability of a lot of neurotransmitter function in the brain and vice versa. It can be disrupted in a whole host of disorders, both that begin neurologically in the brain and/or that begin neurologically in the gut. That reciprocally affect each other in such a way as to make individuals far more neuropsychiatrically impaired or dysfunctional. For example, certain forms of anxiety, chronic fatigue disorder and a variety of different forms of impulse control disorder can all be linked to imbalances in the gut. Even more of the neurodegenerative disorders have been found to have biomarkers that reflect gut dysfunction, which then may affect the production of a number of chemicals in the enteric nervous system that may mirror what’s going on in the brain. Now, we’re beginning to see a greater elucidation of the role of the gut-brain connection in some of the neurodegenerative conditions such as Parkinson’s disease, multiple sclerosis and a host of other neuropsychiatric conditions.
I worked for AstraZeneca for a long time as a pharmaceutical rep for many years and all the things you’re talking about, the parasympathetic, sympathetic and all that stuff, I had to learn all that. I’m thinking of some of the things I’ve read about in the realm or even experienced in terms of hormonally, how much our hormones impact your sense of calm and your cortisol. How big is something like estrogen, estradiol or any of those kinds of hormones to the functioning of your brain?
There are two things that become very important to understand. First, there is a strong neurological to hormonal set of linkages. This is what’s referred to as the neuroendocrine pathways. What we know is that there’s an area of our brain called the hypothalamus, a small collection of cells at the base of the brain that is directly responsible for the mediation and control of the “master gland” the pituitary. The pituitary then controls the endocrine glands for hormonal regulation stability throughout the rest of the body and therefore controls our physiology throughout our lifespan, not only from day to day but across the lifespan. It’s regulating when we come into puberty, when puberty ends, when we then go into adulthood, when we engage menopause, etc., as well as our thyroid function or adrenal function.
The interaction between the hormonal and neurological system is tight and extensive. The other thing that becomes important to understand is that our brain is a sex organ. It is both a target for sex hormones. We know that there are areas of the brain that contain rich concentrations of sex hormone receptors, both receptors for testosterone, as well as estrogen. We know that the brain also has areas that can convert testosterone into estrogen inclusive in the male brain. There’s an old neuroendocrine phrase, it says, “A real man can’t be a real man without female hormone.” In many ways, that’s quite true, but then we also recognize that the structures and functions of the brain are important in regulating sexual development, activity and differentiation. This has become a real boon when we’re looking to, “How does this operate throughout the lifespan? How might the neurological system be involved in some of those more cognitive-behavioral manifestations of our daily behaviors, inclusive, for example, our sexual behaviors?” Can we target the brain? Can we recognize the brain function may be a biomarker for some of these indicators? That’s an exciting place to go.
What brains have in common are their differences. Click To TweetI’m thinking of somebody who had an oophorectomy and then suddenly said she can’t concentrate at all. It’s gone. Does that come back if your ovaries are taken out or you take out certain parts that produce these hormones? Does your brain build new pathways? Are you forever never going to have that again?
It becomes individually variant. It’s not just the gonadal hormones but the steroid hormones in general, the hormones of the adrenal gland, as well as the hormones of the gonads, whether the ovaries or the testes have a fairly profound effect on neurological structure and function. Not only for nerve cells, neurons but also for these other communicative and accessory cells in the brain called glia, they’re embedded with receptors. These hormones can work through non-receptive mechanisms. They can interact with the membranes and other cellular structures of these nerve cells to then not only affect the nucleus of how these cells function, but also affect what’s called non-nuclear mechanisms. Many of these have to deal with the relative threshold for excitability or modulation and that can be evidence itself in cognitive, emotional or sometimes behavioral expressions and variations.
When someone undergoes a fairly profound hormonal shift, whether that’s the shift from childhood into adolescence and puberty, which is what’s referred to as gonadarche. Whether that’s the idea of moving into the perimenopausal or menopausal area, whether someone has had an orchiectomy and had their testicles removed, whether someone has had an oophorectomy and had their ovaries removed, a sudden change in the hormonal constitution can affect the brain. The question is, “How individual, subjective and potent are those effects based upon that particular individual’s vulnerabilities?”
I’ve heard so many instances of people having brain-related things. I had a good friend who passed who had a glioblastoma, which is a serious type of brain tumor. He didn’t live long after they found that. Somebody else told me they had an arachnoid cyst. You can have all kinds of these growths in your head and not even have any impact at all. Something like an arachnoid cyst might not do anything to your brain. Do you study those kinds of things?
We do. I’m an advisor to the brain bank we have at Georgetown. It allows me to utilize some of the neuropathology that I had dealt with years ago as part of my training and understanding of how things could go wrong in the brain. It’s important to understand how things can go right in the brain. There are two interesting ideas here. Number one is that sometimes very small disturbances in brain structure can lead to profound changes in brain function. We think of like, “Nothing is going to happen here,” and then you see an individual becomes wholly dysfunctional and vice versa, where you can see fairly large lesions in the brain, the behavioral and the cognitive effects are not all that great. One of the instances that becomes important is the rate of the growth of whatever the abnormality is.
One thing brain do well is they compensate for a change in their structure and function by reorganizing themselves that’s called plasticity. Very often when you see something like an arachnoid or ependymal cyst, these things are fairly slow-growing so the brain has some time to be able to reorganize its node network activity, to compensate for this mass in the head. Something that’s relatively rapidly growing and something that is invasive and proliferative, for example, an astrocytoma, a glioblastoma multiforme or a head injury can often be devastating in the fact that you’ve not accommodated the mechanisms and time span of plasticity. As a consequence, you’re getting a range of dysfunction and disordering, that’s profound.
I’m thinking of Natasha, Liam Neeson’s wife, she hit her head, her brain swelled and she died from that. If you have something growing like you have an arachnoid cyst, doesn’t your skull eventually get to the point where you can’t hold, even if it’s not a tumor but a liquid type of thing? What happens then?
They’re quite different. Fluid is a bit different because of the fluid nature of that. Where is the fluid going? In the case of a head injury, the problem there is a bleed. There are a number of different types of bleed. You can have an epidural, subdural, internal arachnoidal bleed or you can have a bleed very deeply within the brain tissue itself, as you would find with some types of an aneurysm, or often if you have a hemorrhagic stroke and/or some foreign body in the head. The problem there is you’re losing blood fairly quickly into the brain space and you’re compressing the brain space within the skull. As a consequence of that, what you’re doing is getting herniation of the brainstem and that can lead to autonomic failure and ultimately respiratory and cardiac arrest or what you’re doing is getting what’s called a midline displacement, which then causes a failure of the circulation of the cerebral spinal fluid that rapidly builds up the pressure within the head and then impacts the circulation further within the brain and the whole areas of the brain that are rapidly dying.
Something that is slow-growing, like an ependymal or arachnoidal cyst, or even a slower growing astrocytoma won’t necessarily displace that most brain mass, at least at first. It has to reach a fairly critical mass of both size and displacement in order to then be evidenced by a host of signs and symptoms. The more rapid that something tends to occur in the brain, that is displacing brain tissue causing pressure problems, disrupting blood flow. Characteristically, the more profound and very often, the more catastrophic the results are going to be. Whereas if something is a little more slow-growing, it doesn’t necessarily mean that it could not be catastrophic. It gives you a little bit wider window and a longer period for the development of signs and symptoms, the capability for some plasticity and if it’s diagnosed and assessed appropriately, there’s a proper intervention to eradicate that.
I know so many people who have some form of something either of epilepsy and some of them have Parkinson’s. How much do you do in the research of some of these diseases?
Quite a bit. One of the areas of my work looks at the value and viability of various forms of current and emerging neurotechnologies to afford intervention against what might be in some cases, treatment of refractory, neurological and neuropsychiatric disorders. I’m working with my very good colleague, Prof. Michael Okun at the University of Florida Movement Disorders Clinic. What we’re looking at is how well we can utilize a technology called Deep Brain Stimulation to be able to treat a host of neurodegenerative disorders, neuroinsulted disorders, as well as certain neuropsychiatric disorders.
I’m proud to have been part of something called the Deep Brain Stimulation Think Tank for the past several years, that convened international experts from a variety of fields. From the neurosciences, engineering, commercial entities and from the clinical disciplines of neurology, neurosurgery, psychiatry, habilitative medicine, to focus on what are the latest and greatest developments in the technologies and its methods. Also, what are the latest and greatest developments in the uptake of this technology into medical care, healthcare provision and healthcare support. How insurance is compensating for these techniques and technologies, and what that means for patients who are suffering from a variety of diseases, such as Parkinson’s, dystonia, essential tremor and certain types of treatment-refractory depression.
It has been debated that it might be useful to treat certain types of addiction, chronic pain and increasingly, it’s being examined for use in psychiatric disorders. Some of the pioneering work of Professor Helen Mayberg was examining the viability of using forms of deep brain stimulation to treatment-resistant or intractable forms of depression. Although the clinical trials did not reach a successful endpoint of the trial itself, those cases that were successful, but profoundly successful would certainly indicate that with a bit of refinement in the engineering and the technology and a bit more refinement in the techniques and in-patient selection. This could be a very viable set of interventions for a range of neuropsychiatric conditions.
I’m thinking about how Ritalin works differently. If you need it, it doesn’t buzz you as compared to, if you don’t need it that you get the opposite reaction. I’m thinking about some of the people who’ve been on my show who did some brain treatment, but nothing near what you’re doing where they put the electrodes on your brain to read things or they claimed it would do something to make you feel better. My concern would be, what if you’d have the opposite reaction? Can these things make anybody worse? Have you seen any negative consequences from the deep brain stimulation?
What’s important to note about deep brain stimulation is that it’s medically gate-kept. It requires neurosurgical intervention for implantation. The gatekeeper there is the neurologist and the neurosurgeon. There’s usually an exploratory phase in which electrodes are placed at key identified places within the brain nodes and networks that are involved with other disorders to see if the individual be responsive, number one. Number two, how responsive they will be and if they’re reaching some level of medical improvement that’s going to be clinically satisfying.
At that point, the electrodes are then implanted and the individual characteristically has a recovery that’s both initial and then a bit more gradual. Getting back to a point of reasonably good recovery in a fairly short amount of time. What can be the robust recovery in an intermediate amount of time, a couple of weeks or months, as the brain gets used to the implant, and as the implant is in tuned to be able to take care of more of the dysfunction and make the individual more functional? What can go wrong? It’s neurosurgery. As with any neurosurgery, you worry about the risk of a bleed, risk of infection at the site and the possibility of electrode drift, which is rare, but certainly can happen.
Is it zapping something it shouldn’t be zapping at that point?
One of the positive aspects of the technology is that we’ve become far more sophisticated and much more specific in the type of electrodes that are being used. They’re not singular electrodes with what we call a multi circumferential field, but rather you can direct the current in key directions and distances from the electrodes to be very much more sharp shot rather than buckshot in the stimulation points. We can use more than one electrode and we can also create a system that’s both closed-loop. In other words, we are monitoring brain function of the stimulated brain, as well as an open loop, where we’re then providing input externally inclusive of those things that might come through a variety of different forms like apps or different forms of modulating devices to be able to create a device that’s functional across a range of flexible functionalities. Most of the literature would suggest that we have not seen any real adverse effects that are profoundly repetitive. Can things go wrong? They can. The thing that jumps to mind the most is that it won’t work.
There’s nothing to be like Parkinson’s or something because it zapped something.
What you’re finding is that it’s simply not working to do what it was supposed to do, or it stops working. There’s a number of different ways for that. One thing we see is when we’re dealing with neurodegenerative diseases, the brain keeps degenerating. The brain implant itself does nothing to stop the degeneration. It’s only dealing with the nodes and networks that are there. What happens is that the brain is degenerating to an extent that the implant will no longer be able to compensate for it. That’s one possibility.
The other thing that’s been debated a lot is whether or not individuals incur personality changes and if those personality changes are profound. Our review of the literature and some of the work that we’ve done with a number of colleagues, who’ve been grant-funded to study that issue when looking at it empirically. We’re looking at the real evidence, the evidence for profound personality change, where the individual feels like a different person is quite rare. The instances where we have seen certain changes in an individual’s preference for music or an individual’s behavioral pattern represent the exception rather than the norm.
Our brain is a sex organ. It is a target for sex hormones. Click To TweetThe issue here is that patients do consent to this. It’s not a question of dropping electrodes in people’s heads without their consent. What most patients report is that these technologies give them more of their agency and their autonomy back. It returns to a greater level of functionality individually, socially, culturally and vocationally. We’re seeing the multilevel benefit. What’s happening biologically is beneficial, but also psychologically and socially, these patients are then recovering aspects of their life that were negatively impacted if not robbed by the disease or disorder itself.
It makes me think of the past when everybody was having lobotomies or electroshock therapy. What will we look at in the future, look back on and go, “Look at what they used to do.” You only could do what we know at this point and I think there are so many disorders like schizophrenia and Alzheimer’s. How do you pick what you’re working on? There’s so much to work on when it comes to the brain.
We look back and hindsight is 2020, but we have to be a bit gentle on ourselves at the moment. The reason for that is you can only cash the intellectual and knowledge check based upon the knowledge you got in the bank. It is intellectually or academically referred to as harmless naturalism. We only know what we know and if we’re comfortable in going with what we know, go with it. The real point of neuroethics as a discipline and as a set of practices is that we’ve called for no new neuroscience either we search or its applications without appropriate accompany neuroethics.
Can things go wrong? Yes. Can we get improvements in version 1.0, 2.0, 3.0 or recognize that this particular technique or technology is simply not doing what it’s supposed to do? Sure. That’s the point. We have to be flexible because if the purpose is to develop treatments that are technically right and ethically good to care for the patient, who’s had diminution in their quality of life, in their condition, suffering from the predicament of illness, injury or disease. What you want to be able to do is build some flexibility in your method and your techniques to assure the fixity of purpose of providing that right and good care. A revisionist stance that is self-critical, self-revising and self-correcting is the critical mission of neuroethics as a discipline and practice.
You brought up so many important points. There’s so much that we don’t know, but you have studied this in such great depth. I was so excited to have you on the show. A lot of people will want to know more about how they could follow you. I know you’ve written books, the Neurotechnology in National Security and Defense: Practical Considerations, Neuroethical Concerns. If they wanted to find out more, how could they?
They can simply get in touch with me through my website at Georgetown. That’s James.Giordano@Georgetown.edu. If they want to find out a bit more about my work, go to www.Georgetown.edu and plug in my name, Professor James Giordano, it will take you right to my faculty page. You can see what I and my research group, both singulate at Georgetown, in collaboration with our esteemed international colleagues, they are working on it. Please feel free to get in touch with me. If they want to put in their subject line, Diane Hamilton show and I’ll be happy to get back in touch with them.
They could read 7 books, 21 book chapters and 25 government white papers. I was looking at the list. There’s quite a lot to follow on you. Thank you so much, Dr. Giordano. It’s fascinating what you’re working on and I loved how you shared all your work with us. This was a lot of fun.
Thank you. It was a pleasure and a real honor to be here. I thank your interest in supporting my work.
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I’d like to thank Dr. Giordano for being on the show. He was so fascinating. I could have him here all day just asking questions. I love the research he does. There’s so much to be learned about the brain. I hope that you take some time to check out some of our past guests in case you’ve missed any of our past episodes. We get a lot of amazing guests on this show. You can go to DrDianeHamilton.com to find them. I hope you enjoyed the episode and I hope you join us for the next episode of Take The Lead Radio.
Important Links:
- Dr. James Giordano
- Albert Bandura – Previous episode
- Beau Lotto – Previous episode
- Jürgen Schmidhuber – Previous episode
- Artificial Intelligence and Ethics
- Neurotechnology and National Security and Defense: Practical Considerations, Neuroethical Concerns
- James.Giordano@Georgetown.edu
- www.Georgetown.edu
About Dr. James Giordano
James Giordano, PhD, MPhil, is Chief of the Neuroethics Studies Program, Scholar-in-Residence, leads the Sub-Program in Military Medical Ethics, and Co-director of the O’Neill-Pellegrino Program in Brain Science and Global Health Law and Policy in the Pellegrino Center for Clinical Bioethics; and is Professor in the Departments of Neurology and Biochemistry at Georgetown University Medical Center, Washington, DC, USA. He is also Distinguished Visiting Professor of Brain Science, Health Promotions and Ethics at the Coburg University of Applied Sciences, Coburg, Germany, and was formerly 2011-2012 JW Fulbright Foundation Visiting Professor of Neurosciences and Neuroethics at the Ludwig-Maximilians University, Munich, Germany.
Prof. Giordano currently serves as Chair of the Neuroethics Program of the IEEE Brain Project, and an appointed member of the Neuroethics, Legal and Social Issues (NELSI) Advisory Panel of the Defense Advanced Research Projects’ Agency (DARPA). He has previously served as Research Fellow and Task Leader of the EU Human Brain Project Sub-Project on Dual-Use Brain Science; an appointed member of United States Department of Health and Human Services Secretary’s Advisory Council on Human Research Protections (SACHRP); and as Senior Science Advisory Fellow of the Strategic Multilayer Assessment Branch of the Joint Staff of the Pentagon.
The author of over 290 publications in neuroscience and neuroethics, 7 books, and 15 government whitepapers on neurotechnology, ethics and biosecurity, he is an Editor-in-Chief of the international journal Philosophy, Ethics and Humanities in Medicine; Associate Editor of the Cambridge Quarterly of Health Care Ethics; and Contributing Editor of Frontiers in Human Neuroscience.
His ongoing research addresses the neurobiological bases of neuropsychiatric spectrum disorders; and neuroethical issues arising in and from the development, use and misuse of neuroscientific techniques and neurotechnologies in medicine, public life, global health, and military applications.
In recognition of his work, he was elected to membership in the European Academy of Science and Arts; named an Overseas Fellow of the Royal Society of Medicine (UK); received City University of New York’s Outstanding Alumnus Award; Coburg University’s Gold Medal for Distinguished Achievement, and was awarded Germany’s Klaus Reichert Prize in Medicine and Philosophy.
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