This is the first article in a two-part series describing subject and family perspectives from the central thalamic deep brain stimulation for the treatment of traumatic brain injury using the Medtronic PC + S first-in-human invasive neurological device trial to achieve cognitive restoration in moderate to severe traumatic brain injury, with subjects who were deemed capable of providing voluntary informed consent. In this article, we report on interviews conducted prior to surgery wherein we asked participants about their experiences recovering from brain injury and their perspectives on study enrollment and participation. We asked how risks and benefits were weighed, what their expectations and fears were, and how decisions were reached about trial participation. We found that informed consent and enrollment decisions are fraught. Subjects and families were often split, with subjects more focused on putative benefits and families concerned about incremental risk. Both subjects and families viewed brain injury as disruptive to personal identity and relationships. As decisions were made about study enrollment, families struggled with recognizing the re-emergent agency of subjects and ceding decision-making authority to subjects who had previously been dependent upon them for protection and guidance. Subjects and family members reported a hope for the relief of cognitive disabilities, improved quality of life, normalization of interpersonal interactions, and a return to work or school as reasons for study participation, along with altruism and a desire to advance science. Despite these aspirations, both subjects and families appreciated the risks of the intervention and did not suffer from a therapeutic misconception. A second essay to be published in the next issue of Cambridge Quarterly of Healthcare Ethics—Clinical Neuroethics will describe interviews conducted after surgery, the effects of cognitive restoration for subjects, families, and challenges presented to the social structures they will call upon to support them through recovery. This subsequent article will be available online prior to its formal publication in October 2023.

Central and peripheral biomarkers can be used to diagnose, treat, and potentially prevent major psychiatric disorders. But there is uncertainty about the role of these biological signatures in neural pathophysiology, and their clinical significance has yet to be firmly established. Psychomotor, cognitive, affective, and volitional impairment in these disorders results from the interaction between neural, immune, endocrine, and enteric systems, which in turn are influenced by a person’s interaction with the environment. Biomarkers may be a critical component of this process. The identification and interpretation of biomarkers also raise ethical and social questions. This article analyzes and discusses these aspects of biomarkers and how advances in biomarker research could contribute to personalized psychiatry that could prevent or mitigate the effects of these disorders.

This article examines the emerging possibility of “brain-state transitioning,” in which one brain state is prompted through manipulating the dynamics of the active brain. The technique, still in its infancy, is intended to provide the basis for novel treatments for brain-based disorders. Although a detailed literature exists covering topics around brain-machine interfaces, where targets of brain-based activity include artificial limbs, hardware, and software, there is less concentration on the brain itself as a target for instrumental intervention. This article examines some of the science behind brain-state transitioning, before extending beyond current possibilities in order to explore philosophical and ethical questions about how transitions could be seen to impact on assessment of responsibility and personal identity. It concludes with some thoughts on how best to pursue this nascent approach while accounting for the philosophical and ethical issues.

Evidence suggests that psychedelics bring about their therapeutic outcomes in part through the subjective or qualitative effects they engender and how the individual interprets the resulting experiences. However, psychedelics are contraindicated for individuals who have been diagnosed with certain mental illnesses, on the grounds that these subjective effects may be disturbing or otherwise counter-therapeutic. Substantial resources are therefore currently being devoted to creating psychedelic substances that produce many of the same biological changes as psychedelics, but without their characteristic subjective effects. In this article, we consider ethical issues arising from the prospect of such potential “nonsubjective” psychedelics. We are broadly supportive of efforts to produce such substances for both scientific and clinical reasons. However, we argue that such nonsubjective psychedelics should be reserved for those special cases in which the subjective effects of psychedelics are specifically contraindicated, whereas classic psychedelics that affect subjective experience should be considered the default and standard of care. After reviewing evidence regarding the subjective effects of psychedelics, we raise a number of ethical concerns around the prospect of withholding such typically positive, meaningful, and therapeutic experiences from most patients.

Substantial advancement in the diagnosis and treatment of psychiatric disorders may come from assembling diverse data streams from clinical notes, neuroimaging, genetics, and real-time digital footprints from smartphones and wearable devices. This is called “deep phenotyping” and often involves machine learning. We argue that incidental findings arising in deep phenotyping research have certain special, morally and legally salient features: They are specific, actionable, numerous, and probabilistic. We consider ethical and legal implications of these features and propose a practical ethics strategy for managing them.

People with dementia at times exhibit threatening and physically aggressive behavior toward care staff in residential aged care facilities (RACFs). Current clinical guidelines recommend judicious use of antipsychotic (AP) medications when there is an immediate risk of harm to care staff in RACFs and non-pharmacological interventions have failed to avert the threats. This article examines an account of how this recommendation can be ethically defensible: caregivers in RACFs may have a prima facie ethical justification, in certain cases, to use APs as an act of self-defense. The author examines whether such uses of APs meet the three commonly invoked conditions of ethically permissible acts of self-defense—namely, the conditions of liability, proportionality, and necessity—and argues that such conditions obtain only in a restricted range of cases. The liability constraint can be satisfied if residents are the only ones who are causally responsible for the threats they pose. Further, the condition of proportionality obtains if there is sufficient objective ground to demonstrate that the harm of using the medications does not outweigh the good to be secured. Lastly, the necessity condition obtains when the medications are used at their lowest effective dosage and caregivers in RACFs can reasonably assume that, for the purpose of averting threats posed by residents, the use of APs is the only available course of action. Not meeting any of these fairly stringent conditions renders uses of APs as acts of self-defense in RACFs morally impermissible actions.

A general obligation to make aggregate research results available to participants has been widely supported in the bioethics literature. However, dementia research presents several challenges to this perspective, particularly because of the fear associated with developing dementia. The authors argue that considerations of respect for persons, beneficence, and justice fail to justify an obligation to make aggregate research results available to participants in dementia research. Nevertheless, there are positive reasons in favor of making aggregate research results available; when the decision is made to do so, it is critical that a clear strategy for communicating results is developed, including what support will be provided to participants receiving aggregate research results.

In this article, we focus on the definition and application of the sliding scale of capacity. We show that the current interpretations of the sliding scale confound distinct features of the medical decision, such as its urgency, its severity, or its complexity, that do not always covary. We propose that the threshold for assessing capacity should be adjusted based solely on the cognitive complexity of the decision at hand. We further suggest that the complexity of a decision should be identified based on a patient’s particular cognitive deficits. We utilize the current research on the types of deficits that characterize amnestic dementias and examine which types of medical decisions might be most complex for patients with that type of dementia. We conclude that applying the sliding scale based on individualized judgments of cognitive complexity will improve accuracy of assessment of capacity and enable capable patients to participate in medical decision making.

One health suggests that human and animal health are comparable, but in practice, the concept aligns with the principles of public health ethics. One health ethics, as such, appears to eschew connotations of equality for the natural world. A theory of agency revises that anthropocentric assumption. This article begins with a critique of environmental dualism: the idea that human culture and nature are separate social realms, thus justifying public health as a (unifying) purpose. In response, this article argues that, first, a neuroethics of one health might equally regard humans and (some) animals, which have comparable mental states, as rational agents. Second, rational agency should ground our moral connections to nature in terms of the egalitarian interests we have (as coinhabitants) in the health of the planet. While this article makes a moderate case for interspecific rights (as the first argument asserts), neuroscience is unlikely for now to change how most public institutions regard nonhuman animals in practice. However, the second argument asserts that rational agency is also grounds for philosophical environmentalism. One health ethics, therefore, is a theory of equality and connects culture to nature, and, as such, is a separate, but coextensive approach to that of public health.

Animal models have long been used to investigate human mental disorders, including depression, anxiety, and schizophrenia. This practice is usually justified in terms of the benefits (to humans) outweighing the costs (to the animals). The author argues on utility maximization grounds that we should phase out animal models in neuropsychiatric research. The leading theories of how human minds and behavior evolved invoke sociocultural factors whose relation to nonhuman minds, societies, and behavior has not been homologized. Thus, it is not at all clear that we are gaining the epistemic or clinical benefits we want from this animal-based research.

In recent decades, scientists have begun to identify the brain processes and neurochemicals associated with the different stages of love, including the all-important stage of attachment. Experimental findings—readily seized upon by those bioethicists who want to urge that we sometimes have good reason pharmaceutically to enhance flagging relationships—are presented as demonstrating that attachment is regulated and strengthened by the neuropeptides oxytocin and vasopressin. I shall argue, however, that often what the experimental data in fact show is only that exogenous administration of such chemicals can control and intensify the trappings of attachment, not attachment itself. That this is sometimes overlooked by both scientists and ethicists, is due to attachment being miscategorised as a set of feelings or a drive, rather than as a disposition to think about, feel toward, and behave toward its object in certain distinctive ways.

Pharmacological cognitive enhancement (PCE) refers to the use of pharmaceuticals to improve cognitive function when that use is not intended to prevent or treat disease. Those who favour a liberal approach to PCE trust users to make informed decisions about whether enhancing is in their best interest. The author argues that making informed decisions about PCE requires a nuanced risk-benefit analysis that is not accessible to many users. Presently, the PCE use of prescription medications such as methylphenidate and modafinil is widespread but most commonly happens without medical supervision. Direct and indirect barriers generate a situation where the risks and benefits of PCE are inequitably distributed; as a result, PCE is sometimes not in the user’s best interest. This is likely to also be the case for future pharmaceuticals. As a result, even if PCE pharmaceuticals were equitably distributed, its associated risks and benefits would not be. The article concludes with a discussion of the prospects of the clinical consultation on one hand, and e-health solutions on the other, in ameliorating the situation, arguing for cautious optimism.

The United States Department of Defense has, for at least 20 years, held the stated intention to enhance active military personnel (“warfighters”). This intention has become more acute in the face of dropping recruitment, an aging fighting force, and emerging strategic challenges. However, developing and testing enhancements is clouded by the ethically contested status of enhancements, the long history of abuse by military medical researchers, and new legislation in the guise of “health security” that has enabled the Department of Defense to apply medical interventions without appropriate oversight. This paper aims to reconcile existing legal and regulatory frameworks on military biomedical research with ethical concerns about military enhancements. In what follows, we first outline one justification for military enhancements. The authors then briefly address existing definitional issues over what constitutes enhancement before addressing existing research ethics regulations governing military biomedical research. Next, they argue that two common justifications for rapid military innovation in science and technology, including enhancement, fail. These justifications are (a) to satisfy a compelling military need and (b) strategic dominance. The authors then turn to an objection that turns on the idea that we need not have these justifications if warfighters are willing to adopt enhancement, and argue that laissez-faire approaches to enhancement fail in the context of the military due to pressing and historically significant concerns about coercion and exploitation. The paper concludes with what is referred to as the “least-worst” justification: Given the rise of untested enhancements in civilian and military life, we have good reason to validate potential enhancements even if they do not satisfy reasons (a) or (b) above.

In this series of short essays, stories, poems, and personal observations, Robert A. Burton, neurologist and writer, uses both fiction and nonfiction to explore many paradoxes and contradictions inherent in scientific inquiry. A novelist as well as author of On Being Certain and A Skeptic’s Guide to the Mind, Burton brings story to science and science to story.

While window-shopping for his wife’s birthday, a businessman was struck by a speeding taxi that jumped the curb at 55th and Madison. In the few minutes it took the ambulance to reach the University emergency room, he had lapsed into a coma. Brain imaging revealed a large blood clot compressing the brain. The only hope for his survival was immediate drainage of the clot.