By Xinyuan Chen, Mackenzie Bullard, Christy Duan, Jamilah R. George, Terence Ching, Stephanie Kilpatrick, Jordan Sloshower, and Monnica Williams
In the last two decades, researchers have started to reexamine psychedelics for their therapeutic potential. Though initial results seem promising, the research has a significant shortcoming: the lack of racial and ethnic diversity among research teams and study participants.
In the 1960s, psychedelic substances such as LSD, psilocybin, and mescaline were a major part of American counterculture. Less well-known is that, concurrently, researchers were studying potential therapeutic uses of these mind-altering substances. Unfortunately, psychedelics were classified as Schedule I drugs in 1970, halting research into their therapeutic benefits.
As a psychedelic researcher, I find myself increasingly frustrated by the tendency of the field to make lofty claims about the drugs that stray from the realities and limitations of the data.
For example, psychedelic research that uses neuroimaging employs measures of brain function that are, in fact, quite crude. Typically, one signal in a brain scan can mean many things (amygdala activation can occur when one is scared, happy, observing something salient, etc.).
For this reason, cognitive neuroscientists typically constrain mental activity using behavioral tasks in order to make more educated inferences regarding what is happening in the mind. Yet for some reason, psychedelic scientists believe they can infer mental function from the activity of a few tripping brains under task-free conditions. That is, participants are essentially doing whatever they want in the scanner, making the number of possible inferences one could make nearly infinite. And worse, they base their claims on outdated Freudian theory.
There is a lot of fascinating research about the brain coming out of Stanford University, with some exciting, cutting-edge work being done there. Early last month I reported on the findings made by neuroscientists at Stanford in understanding how mental rehearsal prepares our minds for real-world action. Today, I’ll outline the recent advances made by a team led by Sergiu Pasca, MD, assistant professor of psychiatry and behavioral sciences at Stanford University, and discuss some of the ethical implications of this research.
Pasca’s method enables him to culture cells in order to form brain organoids with robust structures that are not compromised by cells from other parts of the body, thereby allowing him to more accurately replicate distinct brain regions. Doing so provides greater structural organization and also allows him and his team of researchers to better study and understand pathological mechanisms and perhaps one day to examine the molecular, cellular, and circuit levels of a person’s neurons. This is a promising method and a big step toward greater understanding of psychiatric and neurological disease, leading Pasca to declare, “This is our doorway into personalized psychiatry.” At the same time—although these “brain balls” are not brains, nor do they receive sensory inputs from the outside world—it is clear that as scientists progress in both the techniques and complexity of replication, major ethical questions and dilemmas will arise.
Chief among these will undoubtedly be the perennial ethical debate about the ontology of a human being. Is it only physical, material, social—in which case we might think of ourselves as technicians—or is it spiritual, religious, metaphysical—in which case we would more likely consider ourselves custodians? When we speak about attributing rights to animals or consciousness to AI, it is because at bottom we hold some fundamental belief: about dignity, a soul, being, or about what life might mean in a relational or social and emotional sense. This is no different with Pasca’s brain balls; in fact, it is an even more pressing quandary. As Bruce Goldman notes in his article, “One of the most amazing things about their brain balls was that, with not much chemical guidance, they tended to take on a default structure that’s a facsimile of the most evolutionarily advanced part of the brain: the human cerebral cortex, with all six layers you find in a living human brain.” The ethics of growing human organs are one thing, but the ethics of growing brain balls, which might eventually lead to more and more complex synaptic connections followed by even more elaborate renditions of an actual brain, will become especially contentious given the meaning and significance that we associate with the brain—both biologically and existentially.
If you are a skier like me, you likely revelled in watching the alpine skiing events during this years’ Olympic Winter Games held in Pyeongchang, South Korea. Having raced myself when I was younger, I recall the feeling of being in the starting gate with all the anticipation and excitement it brings. But my memories are more than mere recollections of “images” in my head, for I also have vivid muscle memory, and when watching and cheering for Lindsey Vonn and Ted Ligety, I can literally feel my leg muscles contract as if I were on the course myself. Because I skied for so much of my life, my experience now as a spectator brings me back to the hardwired responses that I can call up even to this day in a very intuitive way simply by visualizing a course.
Researchers at Stanford have now corroborated what athletes and psychologists have long believed: that visualizing ourselves performing a task, such as skiing down a race course, or engaged in other routines, improves our performance and increases our success rate. The findings, reported by neuroscientists in Neuron, suggest that mental rehearsal prepares our minds for real-world action. Using a new tool called a brain-machine interface, the researchers have shown how mental learning translates into physical performance and offers a potentially new way to study and understand the mind.
Could this new tool assist us in replicating cognitive responses to real-world settings in a controlled environment? More studies will need to be carried out in order to further test these findings and better understand the results. And one potential point to take into account is that preforming a real action is different than performing the same task mentally via a brain-imaging interface given that one’s muscles, skeletal system, and nervous system are all working in tandem; but, a brain-imaging interface would indeed seem to have very practical implications for those who use prosthetics or are who are paralyzed. As our knowledge of biomechanics and neuroscience advances, as well as our capabilities to interface the two, we may be able to utilize this technology to assist us in creating more life-like prosthetics and perhaps, harnessing the mind’s inborn processes and complex synapses, help others walk again.
Looking toward the future, another interesting subject of research would be to use a brain-imaging interface to study psychoneuroimmunology. We may not have the technology or ability to conduct such a study at the moment, but it seems plausible that in the near future we could develop the tools needed to conduct more rigorous research on the interactions between psychological processes and the nervous and immune systems. If visualizing winning a ski race improves our performance, why not also envisioning good health outcomes: resilient bodies, strong immune systems, plentiful and efficient white blood cells. Simply willing ourselves to health might not be possible, but, to be sure, having a positive outlook has been shown to impact the outcome of disease, while conversely, increased levels of fear and distress before surgery have been associated with worse outcomes. These are but a few examples of the increasing evidence of the mind’s impact on health. It highlights the importance of recognizing a holistic approach that considers the roles of behavior, mood, thought, and psychology in bodily homeostasis. Read More
Professor Robert Sapolsky, a professor of biology and neurology at Stanford University, rightly identifies depression as a particularly crippling disease insofar as it affects one’s very response mechanisms and modes of coping, namely, experiences of gratitude, joy, pleasure—at bottom, some of the key emotions of resistance and healing. In discussing depression, he provides an overview of the biological and chemical elements, touching on the role of neurotransmitters (epinephrine, dopamine, serotonin) in depression, and a summary of the psychological elements (and their relation to the biological); as such, his description focuses primarily on physical and biological explanations. However, to examine depression or any psychological illness in purely physical and biological terms misses a crucial element, namely: human culture, lived experience, and the different modes or methods of social thought. Culture plays a primary role in defining many mental disorders such as schizophrenia and psychosis, and even the symptoms, intensities, or typologies of depression, according to Arthur Kleinman in his seminal Writing at the Margin: Discourse Between Anthropology and Medicine.
Despite these findings, Western biomedicine by and large continues to analyze mental health in clinical and biological terms. This is not insignificant given the statistics:
Approximately 1 in 5 adults in the U.S.- 43.8 million or 18.5% – experiences mental illness in a given year.
Approximately 1 in 5 youth aged 13–18 (21.4%) experiences a severe mental disorder at some point during their life. For children aged 8–15, the estimate is 13%.
Only 41% of adults in the U.S. with a mental health condition received mental health services in the past year. Among adults with a serious mental illness, 62.9% received mental health services in the past year.
Current trends in medicine suggest that the medical community broadly speaking is ill-equipped to adequately tackle this rising trend, especially with regard to the treatment of diverse patients from various cultures, religions, and social circumstances. To best address the problem, the medical community – both on the level of policy and practice -ought to take steps to understand and treat mental illness more holistically.
Think of the last few times you’ve had a very lifelike dream. Running, reading, or having conversations with others, are all activities that might happen during a particularly vivid dream. But would this be considered consciousness? Surely being in a state of sleep is not the same as being in a waking state; but if you are able to communicate, to attend a lecture, perhaps even to give a lecture whilst you sleep, what does this mean in terms of your brain’s activity? Very deep in the sleep cycle, a person may not respond immediately to touch or sound or any other sensory stimulus. That is, they may not wake up, though it cannot be ruled out that an external stimulus might influence the sub-conscious mind and hence their dream. We’ve all had the experience of hearing an alarm “in our dream” which is really our real alarm, yet our mind re-interprets it and incorporates it into our dream until we regain consciousness, i.e., wake up. What if you couldn’t wake up from your unconscious state? And if so, what would this mean for how your brain processes your thoughts? In effect, what would it mean for your lived reality if you could only live in your mind?
Beyond being a fun thought experiment, these may be some very relevant questions now that doctors have treated a vegetative-state patient with an experimental therapy leading him to regain partial consciousness.
It was reported yesterday in National Geographic, Popular Science, the Guardian, and elsewhere that a 35-year-old man who had been in a persistent vegetative state (PVS) for 15 years has shown signs of consciousness after receiving a pioneering therapy involving nerve stimulation. The French researchers reported their findings to the journal Current Biology. Led by Angela Sirigu, a cognitive neuroscientist and director of the Institut des Sciences Cognitives Marc Jeannerod in Lyon, France, a team of clinicians tried an experimental form of therapy called vagus nerve stimulation (VNS) which involves implanting a device into the chest designed to stimulate the vagus nerve. It works by giving off miniscule electrical shocks to the vagus nerve, a critical brain signal that interfaces with parasympathetic control of the heart, lungs, and digestive tract.
What should the future look like for brain-based pain measurement in the law? This is the question tackled by our concluding three contributors: Diane Hoffmann, Henry (“Hank”) T. Greely, and Frank Pasquale. Professors Hoffmann and Greely are among the founders of the fields of health law and law & biosciences. Both discuss parallels to the development of DNA evidence in court and the need for similar standards, practices, and ethical frameworks in the brain imaging area. Professor Pasquale is an innovative younger scholar who brings great theoretical depth, as well as technological savvy, to these fields. Their perspectives on the use of brain imaging in legal settings, particularly for pain measurement, illuminate different facets of this issue.
This post describes their provocative contributions – which stake out different visions but also reinforce each other. The post also highlights the forthcoming conference-based book with Oxford University Press and introduces future directions for the use of the brain imaging of pain – in areas as diverse as the law of torture, the death penalty, drug policy, criminal law, and animal rights and suffering. Please read on!
By Frank Pasquale, Professor of Law, University of Maryland Carey School of Law
Many thanks to Amanda for the opportunity to post as a guest in this symposium. I was thinking more about neuroethics half a decade ago, and my scholarly agenda has, since then, focused mainly on algorithms, automation, and health IT. But there is an important common thread: The unintended consequences of technology. With that in mind, I want to discuss a context where the measurement of pain (algometry?) might be further algorithmatized or systematized, and if so, who will be helped, who will be harmed, and what individual and social phenomena we may miss as we focus on new and compelling pictures.
Some hope that better pain measurement will make legal disability or damages determinations more scientific. Identifying a brain-based correlate for pain that otherwise lacks a clearly medically-determinable cause might help deserving claimants win recognition for their suffering as disabling. But the history of “rationalizing” disability and welfare determinations is not encouraging. Such steps have often been used to exclude individuals from entitlements, on flimsy grounds of widespread shirking. In other words, a push toward measurement is more often a cover for putting a suspect class through additional hurdles than it is toward finding and helping those viewed as deserving.
Of Disability, Malingering, and Interpersonal Comparisons of Disutility (read on for more)
The prevalence of chronic pain is staggering. The Institute of Medicine reported in 2011 that 100 million Americans suffer from chronic pain – more than those with heart disease, cancer and diabetes combined. The report also highlights that the annual costs for medical care, lost wages and productivity is more than $600B. These enormous personal and societal costs of chronic pain has driven an effort to “prove” if and how much pain an individual is suffering from for health care providers, insurance companies and legal actors. This is challenging because pain is a personal and subjective experience. Ideally, self report would be sufficient to establish the “ground truth” of the pain experience.
However, some are not able to provide self reports accurately, and the potential financial gain associated with claims of pain has tarnished the perceived authenticity of subjective reports. This has led some to develop brain imaging-based tests of pain – a so-called “painometer.” Yet, current technologies are simply not able to determine whether or not someone has chronic pain. Here, I consider specifically how we could develop a brain-imaging based painometer – and whether we would want to do so. As we ask: “Can we do it?,” we should always ask, “Is this the right thing to do?”
This conference was the culmination of CLBB’s year of work on pain neuroimaging and law. As the first CLBB-Petrie-Flom Center Senior Fellow on Law & Applied Neuroscience, I focused on pain because it is one of the largest social, economic, and legal problems that can be addressed through new insights into the brain. Pain imaging can be a test case for how neuroscience can contribute positively to law and culture. (Full conference video proceedings are available here.) Please read on below! Read More