Is memory enhancement right around the corner?

By Ryan Purcell

“Everyone has had the experience of struggling to remember long lists of items or complicated directions to get somewhere,” Dr. Justin Sanchez of DARPA said in a recent press release. “Today we are discovering how implantable neurotechnologies can facilitate the brain’s performance of these functions.” The US Department of Defense is interested in how the brain forms memories because hundreds of thousands of soldiers – or “warfighters” as they are now called – have suffered from traumatic brain injury (TBI) and some have severe memory problems. Beyond the military, TBI is a major public health concern that affects millions of Americans as patients and caregivers and is incredibly expensive. A breakthrough treatment is needed and for that, ambitious research is required.

But does this research agenda end at treating disease, or could these findings also be applied to memory enhancement goals?

Beyond helping us to grab all the items on the grocery list and find the car in the parking lot, our memories fundamentally help us to form our sense of identity and personal narrative. It is a common observation in profound dementias and Alzheimer’s disease, that family members feel like their loved one who has lost the ability to recall recent events or names or to form new memories is no longer the same person they once were. While this basic truth about the importance of memory is persuasive as an argument for the significance of this research, it also brings the risks involved sharply into focus: tinkering with an individual’s memories and their ability to form them can have the effect of profoundly altering their identity and sense of self.

In the past, DARPA has been very open about its goals for human enhancement so it is fair to consider the development of memory enhancement as a possible, if not likely, outcome of this research. The umbrella program at DARPA, called RAM for Restoring Active Memory (and invoking the term for computer memory) is what Dr. Sanchez was commenting on in the opening lines of this post. Examples of RAM projects can be found here and here and the stated goal of the project is to develop an implantable (i.e. inside-the-skull) device that can restore an individual’s memory abilities. This is notable because to the public, restoring impaired memory and enhancing memory function are seen as very different aims. In a recent Pew Research survey, 67% of US adults taking part in the study felt that a device that enhances ability far beyond that of any human known to date is taking technology too far and 69% are worried about technology like this.

An improved, sharper, more reliable memory would be a useful improvement, right? If you give me the option between two computers and one has a much better memory, that one will always be my choice. The reality for human beings is probably not so simple. Consider Jill Price, one of only a few people in the world known to have Highly Superior Autobiographical Memory (HSAM). In the original description of her case, Price seems surprisingly ordinary in many ways. She earned mediocre grades in school and worked off and on as an office assistant after college. However, her autobiographical memory is astounding. Name a date after 1974 and she can tell you what day of the week it was, what she did that day, if any notable public events occurred on that date, and what the weather was like. Most of us would struggle to recount what we did on any given day last month, let alone decades ago. It is surprising, then, that her incredible memory did not make her extraordinarily successful in school or her career and, in fact, she described her memory as being rather burdensome, preventing her from letting anything go. After Price’s case became known to researchers, others came forward to be studied as well. After thoroughly vetting the volunteers, and studying the most likely HSAM cases, researchers concluded that these extraordinary autobiographical memory abilities were not paired with a more generalized genius or even improved memory in other areas. These cases highlight the critical balance between remembering and forgetting that probably goes a long way in helping us get through our daily lives.

We also know from nonhuman animal studies that enhanced memory does not always lead to positive outcomes. At brain synapses, NMDA receptors are critical mediators of neuroplasticity. Genetically increasing the expression of a subunit of the NMDA receptor, NR2B, in mice improved the animals’ learning and memory across multiple paradigms. However, further testing demonstrated that these animals were also were more sensitive to some painful stimuli, highlighting the possibility that it may be difficult to selectively augment one neural process in a purely positive way. This, however, is just one example of a memory enhancement study. Additional studies in rodents have found that spatial memory can be enhanced by stimulating the entorhinal cortex and some of the negative effects of TBI on learning and memory can be ameliorated with stimulation of the medial septal nucleus, an input to the hippocampus. Patients suffering from intractable epilepsy have made an enormous contribution to neuroscience for several decades by volunteering for intracranial cortical and deep brain stimulation studies. Evidence from human studies is now emerging to suggest that stimulation of memory structures and pathways in the medial temporal lobe can also enhance certain types of memory.

If an intracranial memory-enhancing device is developed in the near future, who should get it (and who would get to make that call)? To me, the risk benefit calculation is much easier than a similar one on cognitive enhancing pills. Opening up the skull is a rather significant barrier that will likely keep all but those who need it the most from considering such an intervention for enhancement (versus therapeutic purposes). Regarding enhancement, if soldiers were to receive implanted devices aimed at improving their performance in combat, what happens when their tour of duty is completed, or when they retire? Moreover, during initial testing of any devices in healthy subjects, there are significant and unique consent issues in the military due to power imbalances between officers and subordinates. Even in relatively recent history, there have been serious problems in human subjects research in the military, which have come to light as documents are de-classified.

There are other, non-invasive neurotechnologies also in development that have been discussed here and elsewhere before and it’s likely that the technology will only become less invasive, smaller and, like everything else, wireless in the near future. In addition to helping TBI patients recover memory abilities, DARPA’s warfighter enhancement goals probably center around improving memory under combat conditions of extreme stress and fatigue, factors that can obviously impair memory performance. “Military personnel carry a growing responsibility to recount, report and act upon knowledge gleaned from previous experiences, and how well those experiences are recalled can make all the difference in how well these individuals perform in combat and other challenging situations,” Dr. Sanchez explained in a recent press release on the program. Human errors were blamed for the deadly US airstrike on a Doctors Without Borders hospital in Afghanistan last year that claimed 42 lives. Clearly, there are also potential costs for not pursuing enhancement technology.

Military personnel are not the only professionals who need to perform at a high level under difficult conditions. Could surgeons and airline pilots also benefit from memory enhancing technology? These examples are often invoked in enhancement discussions because this type of work impacts other people’s lives and mistakes can be fatal. Therefore, technology that the military finds to be useful will likely have applications elsewhere in society. Consider another DARPA project, the Internet. Also as the technologies are improved (smaller, less invasive, more affordable), it’s likely that there will be a nontrivial consumer market.

Other DARPA-funded neuroscience research has also been discussed previously on this Blog. That time, the researcher was studying the way the brain interprets narrative storytelling and seemed genuinely uneasy about the possibilities for advanced (neuro)propaganda coming from his work. Here, there is a clear potential medical benefit to a group of people who currently have a dearth of treatment options. Nonetheless, the synopsis from DARPA’s own PR team is as follows:

“The study aims to give researchers the ability to “read” the neural processes involved in memory formation and retrieval, and even predict when a volunteer is about to make an error in recall. The implanted electrodes also provide a means of sending signals to specific groups of neurons, with the goal of influencing the accuracy of recall.”

I, for one, am not overly thrilled about the idea of government scientists “influencing the accuracy of [my] recall” but maybe I just went a bit overboard with Stranger Things. To be clear, understanding the neural signatures of memory encoding, and how that process goes awry after brain injury, is fundamentally important work for basic and clinical neuroscience. Yet as memory enhancement research moves forward, it will be important to continue to keep neuroethics in mind which, surprisingly, is not the norm. A recent review article of the field never once even gives a nod to current or future ethical concerns. Given the fundamental link between memory and identity, research in this area should proceed with consideration of potential nonphysical harms of memory interventions. Finally, as noted above, the Internet as we know it today is in large part thanks to DARPA research, which is a bit ironic because now, with the Internet at our fingertips, who needs to remember anything anymore?

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Purcell, R. (2016). Is memory enhancement right around the corner? The Neuroethics Blog. Retrieved on , from http://www.theneuroethicsblog.com/2016/12/is-memory-enhancement-right-around.html

Meet Tomorrow's World: A Meeting on the Ethics of Emerging Technologies

By Marcello Ienca

Marcello Ienca, M.Sc., M.A., is a PhD candidate and research assistant at the Institute for Biomedical Ethics, University of Basel, Switzerland. His current projects include the assessment of intelligent assistive technologies for people with dementia and other neurocognitive disabilities, the regulation of pervasive neurotechnology, and the neurosecurity of human-machine interfaces. He is the chair of the Student/Postdoc Committee of the International Neuroethics Society and the current coordinator of the Swiss Network for Neuroscience, Ethics and Law.

Technology is rapidly reshaping the world we live in. In the past few decades, mankind has not significantly changed biologically, but human societies have undergone continuous and unprecedented developments through technological innovation. Today, most human activities—from messaging to geolocation, from financial transactions to medical therapies— are computer-mediated. In the next decades, the quantity and variety of activities mediated by digital technology is bound to increase exponentially. In parallel, with advancements in artificial intelligence (AI), robotics and microcomputing, the friction between man and machine is set to vanish and the boundaries at the human-machine interface are bound to blur. In an attempt to anticipate our technological futures as well as their impact on our societies and our systems of values, the International Neuroethics Society (jointly with the Temporal Dynamics of Learning Center, the Science Collaboratory of the University of California, San Diego, and the National Science Foundation) sponsored a public event on the Ethics of Emerging Technologies as part of the 2016 annual INS meeting in San Diego, California. The event was organized by INS President Judy Illes, INS Executive Director Karen Graham, Dr. Rachel Wurzman of the INS Public Session Program Committee and Prof. Andrea Chiba, Dr. Roger Bingham and Prof. Deborah Forster of UCSD. A panel of international experts in various areas of science and ethics gathered in San Diego on November 9 to discuss various critical issues emerging at the human-machine interface with possible disruptive implications for ethics and society. The first perspective was provided by Dr. William D. Casebeer, career intelligence analyst and Lieutenant Colonel in the US Air Force. His short talk proposed an interesting analogy between pervasive technology and the art of storytelling to show how technology could be actually used, in the near future, to raise empathy, deliver personalized experiences and facilitate human interaction.

Image courtesy of Wikimedia Commons

The second talk, delivered by Dr. Kate Darling, research specialist at the MIT Media Lab, focused on the near-term effects of robotic technology, with a particular interest in their legal, social, and ethical issues. Her analysis took a first step from the common observation that people often treat robots like they are alive, despite consciously knowing that they are not living beings in any significant sense. A paradigmatic example is the confirmed report of soldiers having held funerals for fallen robots. The reason for that, Darling argued, presumably stems from the fact that robots embody physicality and movement, two qualities that are essential to animated beings. This phenomenon shows that robots can also be effectively used for supporting empathic activities such as therapy, assistance and social interaction. However, Dr. Darling also anticipated possible risks associated with robotics-assisted activities, in particular the risk that such engaging technologies may become manipulative technologies. This risk appears particularly relevant in the context of using anthropomorphic, or at least animalomorphic, assistive robotics for people with neurocognitive disabilities, including Paro and iCat. Due to their cognitive impairments, users of these technologies may lack the capacity to discern the robotic nature of these devices, and hence fail to draw the line between the biophysical and in-silico world.

Similar risks of physical-digital conflation were addressed at a deeper neurobiological level by Prof. Mayank Mehta, lab head at the W. M. Keck Center for Neurophysics at University of California, Los Angeles. His research results showed that a brain region involved in spatial learning produces a pattern of activity when it processes virtual reality (VR) that is completely different than the pattern of activity produced when it processes activity in the real world. In particular, more than half of all neurons in the space mapping brain region shut down when processing VR and the remaining maps are scrambled. In addition to space mapping, this part of the brain is crucial for many forms of learning and is directly involved in several neurological diseases invluding Alzheimer's disease, epilepsy, post-traumtic stress disorder (PTSD) and depression. Mehta's research has also shown that this part of the brain is very plastic, even in adults and seniors, suggesting that abnormal activity patterns in VR could potentially rewire this part of the brain. As the use of VR is rapidly becoming pervasive for communication and entertainment purposes, Mehta emphasized the urgent need of understanding the long-term consequences of VR use on this improtant and delicate part of the brain.



VR and assistive robotics not only raise the risk of eroding our awareness of the physical-digital distinction, but raise privacy and identity concerns, too. In fact, emerging technologies can also be used to collect personal data and even influence a person’s behavior. These privacy risks were well exemplified by Jay Giedd, Professor of Psychiatry at the University of California, San Diego. He introduced the notion of “penetration technology” to refer to the phenomenon where technology advances faster than society can adapt in terms of governance and regulation. For example, he reported that the number of events in which people participate on Facebook was demonstrated to be a good predictor of depression. However, he observed that conducting big-data research on large volumes of publicly available information on social media opens up fundamental research ethics dilemmas. In particular, there is an ethical issue of privacy and confidentiality: is a person’s informational privacy respected if researchers mine data from his or her social media profile without explicit authorization? On the one hand, the answer to this question seems to be affirmative because that information was posted publicly by the user and after acceptance of the social media’s terms and conditions. On the other hand, however, no explicit request for the acquisition of informed consent was advanced by the researchers. In parallel, neuroscientist and entrepreneur Vivienne Ming emphasized the positive dimension of such big-data trends: although collecting large volumes of data for research purposes may be questionable from a privacy perspective, it can also be extremely beneficial for science and society. Going back to Giedd’s example, the application of predictive analytics techniques to large volumes of social media data might predict depression or a manic episode, possibly saving lives that could not be saved otherwise.

Image courtesy of Jisc

These critical ethical questions were further analyzed in depth by Dr. Hannah Maslen and Prof. Julian Savulescu of the University of Oxford. Dr. Maslen called for an open debate on determining the principles that should govern the use of health technology in educational contexts. She introduced the idea of a child’s “right to future openness” to emphasize the duty of parents to keep a sufficient number of options open for their children. Moving from the educational context to a larger societal perspective, Prof. Savulescu underlined the role of human morality in enabling social interaction within groups. From his perspective, technology can be coopted as an efficient tool to achieve these prosocial goals, particularly if it is used to provide cognitive and moral enhancement both at the individual and collective level. Such enhancement, however, may cause structural transformations to critical aspects of our modern societies, including the political dimension.

On the whole, all panelists were optimistic about future advancements in technological innovation and dissemination. However, they called for a cooperative effort to anticipate the ethical and social implications of emerging technologies and to open a public debate on these issues. This debate has been successfully initiated with the Meeting on the Ethics of Emerging Technologies. It is now up to all of us to shape the technological future we want to live in.

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Ienca, M. (2016). Meet Tomorrow's World: A Meeting on the Ethics of Emerging Technologies. The Neuroethics Blog. Retrieved on , from http://www.theneuroethicsblog.com/2016/12/meet-tomorrows-worlda-meeting-on-ethics.html

"Inflammation might be causing depression": Stigma of mental illness, reductionism, and (mis-)representations of science

by Katie Givens Kime

Image courtesy of Flickr

“Is depression a Kind of Allergic Reaction?” Provocative headlines like these appear throughout popular media. Besides misrepresenting scientific findings, such journalistic coverage impacts perceptions of mental illness, as well as expectations of those seeking treatment. In last month’s Neuroethics in the News talk, Dr. Jennifer Felger, from Emory’s Department of Psychiatry and Behavioral Sciences, shared her experiences and insights on the translation (and mistranslation) of research by journalists. In relating the story of her own interactions with the media, Felger emphasized the complex and varying transactional relationships between journalists and scientists. The impact of such coverage carries notable neuroethical dimensions, potentially affecting the capacity for agency and/or aspects of a sense of self for a person experiencing mental illness.

The work of Felger and others on the role of inflammation in depression emerges from widespread observations that stress and other psychological experiences, particularly chronic stress, can weaken immune responses, leaving individuals more susceptible to illness. Such vulnerability can lead to common illnesses, like colds and flus, or even contribute to major illnesses, like cardiovascular disease, cancer, and inflammatory illnesses. On the other hand, once the immune system is activated by disease, stress, trauma, or even treatments for medical illness (e.g. chemotherapy), activated immune cells can release inflammatory mediators like cytokines. These mediators, along with the immune cells, can move into the brain, affecting neurotransmitter function, leading to behavioral changes, and even causing clinical depression.

Image courtesy of GetStencil.com 

The particular area of research for Felger and some of her colleagues involved examining the mechanisms of cytokine action on the brain, and determining how cytokine action can lead to specific depressive symptom clusters. Felger’s findings suggest that for patients with increased inflammation (including patients with depression), anti-inflammatory or pro-dopaminergic treatment strategies might target decreased corticostriatal connectivity and improve motivational and motor deficits.

In essence, Felger and her colleagues found evidence that suggests a higher level of inflammation increases the likelihood of depression. Furthermore, patients with depression who have higher levels of inflammation may experience different symptoms of depression, which are related relate to the effects of inflammation on the brain. Publication of these findings led to articles in news outlets, for example, “Inflammation may be causing depression in about one-third of patients?” Although such articles did emphasize that depression is a heterogeneous disorder with wide variations in symptoms, they often oversimplified the nuances of Felger’s research regarding the relationship between inflammation and depression. More importantly, in this particular article, unpublished observations on the frequency of depressed patients with increased inflammation, which is highly sample and study- specific, was emphasized without attention to supporting scientific literature. Promotion of oversimplified and preliminary statements by the media can bias interpretation of the findings by other scientists, health providers, and the general public alike.

During her talk, Felger shared how her recent experience with the media has changed the way in which she considers framing and phrasing her research for scientific journals. She suggested that it can be helpful to anticipate the types of quotes the press will use. Having a rough sense of the terms that journalists are likely to grab can preclude some misrepresentations, reductionisms, and reinforced stigmas of mental illness by the media. Knowing the sort of coverage a journalist is seeking is important to help a researcher determine how they should best respond. Felger noted that a piece seeking to narrate the “general movement in the field” is much harder to write well than a piece focused on a singular study or set of findings. With more general overviews, cherry-picking of particular findings or implications is more likely to happen, resulting in higher incidences of misrepresentations.

Another helpful strategy that Felger highlighted is utilizing institutional resources for communicating research. In Felger’s case, working with Emory’s Woodruff Health Sciences Center (WHSC) Office of Research Communications was highly productive. A staff member from that office collaborated with Felger on a press release, headlined “Inflammation linked to weakened reward circuits in depression.” Despite using such institutional resources, Felger is clear that she and her colleagues have no foolproof way to avoid misrepresentations of their research findings.

Fortunately, some journalists are aware of their responsibility to represent research findings accurately. In Felger’s case, some journalists shared drafts of their story before they went to press, seeking a back-and-forth collaboration to ensure ethical reporting. For example a recent article from Oprah.com in which Dr. Felger was interviewed, “Is this why you feel bad? 6 issues tied to inflammation.”

In Felger’s experience, emails and messages to her from members of the general public also highlighted the stakes of these matters. In the changing terrain of health information, clinicians and researchers face the inevitable complexity that most patients search the internet for information about their symptoms or diagnoses. Moreover, patients will directly contact the researchers themselves. Felger noted the difficulty and importance of crafting ethically appropriate responses when members of the public sought interaction with her on her research. Such a situation is even more ethically fraught when the researcher is an investigator and not a physician — in such cases, researchers must work with physicians to construct ethically responsible responses.

Image courtesy of Wikimedia Commons

One example of the stakes of these issues is a piece published by the BBC about three months ago: “Depression: A revolution in treatment?” The article is a relatively standard representation of how the media has covered the topic of links between depression and inflammation, though it is hardly the biggest culprit in terms of misrepresentation or distortion of research findings. Notably, the text of the piece is interrupted with a quiz titled “Could I be depressed?” and a first question, “In the last two weeks: How often have you been bothered by having little interest or pleasure in doing things?” Such interactive features are quite obvious indicators of the readership for such media pieces, and the dangers involved. The disclaimer on the quiz echoes these concerns, “If you are having trouble understanding any of these questions, or at any point you start to feel distressed, please stop and seek the advice of a medical professional. See the links below for organisations that may be able to help you.” Though such disclaimers are included, is it appropriate to be encouraging self-diagnosis through such features?

The neuroethical dimensions to these matters extend beyond clinically and ethically appropriate communications with individual members of the public, however. Perhaps the most pronounced neuroethical matters at stake are the reinforcement of stigmas and the prioritizing of biological etiology. Felger shared her experience of the rapacious hunger for biological explanations of mental illness. She received message after message from people thanking her for “finding the answer” to their depression. Similarly, in the BBC article, an individual diagnosed with severe depression is quoted as saying, “If there was a way to say depression was a physical problem, I think it would make a massive difference, I think people would treat depression as something that is not made up and going on in the head. It would be seen as a genuine condition, it would validate a lot of people's feelings.” It is a summation of how the media’s portrayal of the connection between inflammation and depression not only implies a mechanistic solution to mental illness, but also reinforces the message that biological explanations (rather than lifting of stigma) is the way for an individual suffering mental illness to be released from blame for their illness.

The current trajectories of neuroscientific research suggest we are likely to see more and more exciting and important findings emerge as to the embodied, biological aspects of mental illness. It does not inevitably follow, however, that such findings must be interpreted and communicated in ways that split the nature of mental illness into a false binary that equates biological etiologies with release from blame, and equates psychological etiologies with blame-worthiness. Felger noted how public discourse about mental illness in the U.S. (as well as BRAIN projects on a national level) remains stuck in outdated debates about biological explanations for mental illness.

Moving forward, an important role for neuroethics is watching for how research findings communicated in the popular media contribute, for good or for ill, to the ways in which individuals understand and relate to their own health, in all its complexities.

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Kime, KG. (2016). "Inflammation might be causing depression:" Stigma of mental illness, reductionism, and (mis-)representations of science. The Neuroethics Blog. Retrieved on , from http://www.theneuroethicsblog.com/2016/12/inflammation-might-be-causing.html