Peter B. Reiner

University of British Columbia | UBC · National Core for Neuroethics

Ubiquitous cognitive biases hinder optimal decision making. Recent calls to assist decision makers in mitigating these biases—via interventions commonly called “nudges”—have been criticized as infringing upon individual autonomy. We tested the hypothesis that such “decisional enhancement” programs that target overt decision making—i.e., conscious,...

How might empirical research enrich our understanding of the nature of autonomy? This chapter sets out two main insights gleaned from our interdisciplinary work into this question. The first concerns critical reflection, a fundamental internalist condition for autonomy, and its relation to how a person's beliefs and values relate to reality. We set...

Background: The Canadian public has repeatedly expressed its desire for advance requests for Medical Assistance in Dying (MAiD) after dementia diagnosis, yet MAiD practitioners' willingness to accede to such advance requests is unknown. This study explores the extent and nature of any gap between the public's desire for, and practitioners' willingn...

We are living in a digital era, a time of Alexa and AlphaGo, of Facebook and Fitbit, of Twitter and TikTok. Remarkable opportunities lie ahead: smart technologies in the home, the convenience of deliveries by drone, the pleasure of riding to work in an autonomous vehicle. There are, of course, ethical implications to these advances. There are secur...

Ethical discourse draws upon information from various disciplines to promote normative conclusions. In this chapter, we review one particular method—the contrastive vignette technique (CVT)—that has been fruitfully used as a quantitative means of exploring public attitudes towards ethically challenging issues. The chapter serves as a practical guid...

Given the ubiquity and centrality of social and relational influences to the human experience, our conception of self-governance must adequately account for these external influences. The inclusion of socio-historical, externalist (i.e., “relational”) considerations into more traditional internalist (i.e., “individualist”) accounts of autonomy has...

Advances in psychology and neuroscience have elucidated the social aspects of human agency, leading to a broad shift in our thinking about fundamental concepts such as autonomy and responsibility. Here, we address a critical aspect of this inquiry by investigating how people consider the socio-relational nature of their own agency, particularly the...

Full set of screens presented to the respondents.

Excel file containing all data included in this study.

The neural basis of human memory is incredibly complex. We argue that the diversity of neural systems underlying various forms of memory suggests that any discussion of enhancing 'memory' per se is too broad, thus obfuscating the biopolitical debate about human enhancement. Memory can be differentiated into at least four major (and several minor) s...

The neural basis of human memory is incredibly complex. We argue that the diversity of neural systems underlying various forms of memory suggests that any discussion of enhancing 'memory' per se is too broad, thus obfuscating the biopolitical debate about human enhancement. Memory can be differentiated into at least four major (and several minor) s...

Supplementary data are available at JLBIOS online.

Between-subject design surveys are a powerful means of gauging public opinion, but critics rightly charge that closed-ended questions only provide slices of insight into issues that are considerably more complex. Qualitative research enables richer accounts but inevitably includes coder bias and subjective interpretations. To mitigate these issues,...

ABSTR ACT How does the public view the offer of a biological treatment in lieu of prison for criminal offenders? Using the contrastive vignette technique, we explored this issue, using mixed-methods analysis to measure concerns regarding changing the criminal's personality, the coercive nature of the offer, and the safety of the proposed treatment....

Thoughtful use of ubiquitous technology can improve mental ability more than drugs and devices, say Nicholas S. Fitz and Peter B. Reiner.

Strategies for improving individual decision making have attracted attention from a range of disciplines. Surprisingly, neuroscience has been largely absent from this conversation, despite the fact that it has recently begun illuminating the neural bases of how and why we make decisions, and is poised for further such advances. Here we address empi...

Introduction: Freely accessible online tests for the diagnosis of Alzheimer's disease (AD) are widely available. The objective of this study was to evaluate these tests along three dimensions as follows: (1) scientific validity; (2) human-computer interaction (HCI) features; and (3) ethics features. Methods: A sample of 16 online tests was ident...

In order to gain insight into the public’s perspective on using the minimally invasive technique transcranial direct current stimulation (tDCS) as an enhancement tool, we analyzed and compared online comments in key popular press articles from two different periods (pre-commercialization and post-commercialization). The main conclusion drawn from t...

In order to gain insight into the public’s perspective on using the minimally invasive technique transcranial direct current stimulation (tDCS) as an enhancement tool, we analyzed and compared online comments in key popular press articles from two different periods (pre-commercialization and post-commercialization). The main conclusion drawn from t...

Critical thinking about ethics in neuroscience can be a powerful force in enabling research and translating results meaningfully for society. This chapter provides four examples of such an empowered approach to neuroscience. The authors discuss how upfront consideration of the societal implications of advances in neuroscience can shape the use of a...

The excitement around tDCS as a technique for changing human brains is palpable: tDCS is relatively safe, relatively inexpensive, and relatively effective, in particular as a means of enhancing normal brains. It is also relatively easy to build a device at home, and the do-it-yourself community is latching on to the latest scientific advances with...

Maslen and colleagues offer an excellent model for regulating cognitive enhancement devices (CEDs), and we largely endorse their approach of extending medical device policy to include CEDs. Maslen et al. argue that since the risks and benefits of CEDs can be identified, consumers are best placed to evaluate the impact of these effects on their own...

The ambiguity regarding whether a given intervention is perceived as enhancement or as therapy might contribute to the angst that the public expresses with respect to endorsement of enhancement. We set out to develop empirical data that explored this. We used Amazon Mechanical Turk to recruit participants (N = 2776) from Canada and the United State...

The debate over the propriety of cognitive enhancement evokes both enthusiasm and worry. To gain further insight into the reasons that people may have for endorsing or eschewing pharmacological enhancement (PE), we used empirical tools to explore public attitudes towards PE of twelve cognitive, affective, and social (CAS) domains (e.g., attention,...

Vigorous debate over the moral propriety of cognitive enhancement exists, but the views of the public have been largely absent from the discussion. To address this gap in our knowledge, four experiments were carried out with contrastive vignettes in order to obtain quantitative data on public attitudes towards cognitive enhancement. The data collec...

Primary care physicians are gate keepers to the medical system having a key role in giving information and prescribing drugs to their patients. In this respect they are involved in claims of patients/ clients for pharmacological Cognitive Enhancement (CE). Therefore, we studied the knowledge of primary care physicians about CE and their attitudes t...

Transcranial direct current stimulation (tDCS), a simple means of brain stimulation, possesses a trifecta of appealing features: it is relatively safe, relatively inexpensive and relatively effective. It is also relatively easy to obtain a device and the do-it-yourself (DIY) community has become galvanised by reports that tDCS can be used as an all...

Ubiquitous cognitive biases hinder optimal decision making. Recent calls to assist decision makers in mitigating these biases-via interventions commonly called "nudges"-have been criticized as infringing upon individual autonomy. We tested the hypothesis that such "decisional enhancement" programs that target overt decision making-i.e., conscious,...

The ongoing discussion regarding the propriety of cognitive enhancement is, at its core, biopolitical. In an attempt to understand the underlying issues, it is instructive to view the subject through the perspectives of those at the extremes – the Transhumanists who enthusiastically support the development of cognitive enhancement and the Bioconser...

Research into the efficacy and safety of cognitive enhancers for recreational or lifestyle use has not been done. Should society pay for studies that might improve the lives of already healthy people?

This article reviews the scientific advances and cultural trends that have resulted in the rise of neuroessentialism. It provides a portrait of the varieties of neuroessentialist thoughts that draw on the current understanding of brain function, and then uses these insights to see how neuroessentialist thinking might alter the mores of society. It...

Background / Purpose: Discourse in neurolaw sometimes characterizes (or speculates about the future status of) retributivism as the intuitive and preferred punishment theory among the general public. However, no validated psychological scale has yet been created to measure endorsement of retributivism, and thus we set out to construct one. Main...

Neuroscience has substantially advanced the understanding of how changes in brain biochemistry contribute to mechanisms of tolerance and physical dependence via exposure to addictive drugs. Many scientists and mental health advocates scaffold this emerging knowledge by adding the imprimatur of disease, arguing that conceptualizing addiction as a “b...

Autonomy, the ability to make decisions for ourselves about ourselves, is among the most prized of human liberties. In this review we reconsider the key conditions necessary for autonomous decision making, long debated by moral philosophers and ethicists, in light of current neuroscientific evidence. The most widely accepted criteria for autonomy a...

Banja (2011) nimbly analyzes how a particular strain of conceptual myopia corrodes the rigor of “moral conservative” arguments in bioethics, particularly on the topic of human enhancement. We find his prototypist angle meritorious, but demur on a key conclusion: that virtue essentialism’s “prospects for remaining popular, especially among nonbioeth...

Physician Attitudes to Patients' Cognitive Health. Over 80% of physicians reported not routinely probing cognitive function in patients aged 25-40, and 65% of physicians also did not routinely probe cognitive function in patients' aged 41-59. However, 79% of the physicians surveyed routinely probe cognitive function in patients' aged 60 and above....

Selected Comments on Physician Views on Prescribing Cognitive Enhancers. (0.03 MB DOC)

Physicians' Comfort Rating with Prescribing Cognitive Enhancers to 25-year-old Patients in Different Scenarios. Figure S2 compares how physicians rated their comfort levels with prescribing the described cognitive enhancer to three 25-year-old patients in 3 different scenarios: one who came in simply reporting symptoms of cognitive dysfunction (no...

Comments on Prescribing Cognitive Enhancers to a 25-year-old, Assuming Long-term Favorable Safety Data. Physicians were asked to freely respond on the question of prescribing the hypothetical cognitive enhancer to a 25-year-old patient assuming all the safety concerns they previously had have been laid to rest with long-term convincing data. Their...

Stratified Analysis of Physicians' Comfort Rating with Prescribing Cognitive Enhancers to Patients. Mean physician comfort rating with prescribing the hypothetical cognitive enhancer to patients of differing ages stratified by physician age, sex, and familiarity with cognitive enhancers. (A) There was no significant difference between physicians in...

Male and Female Physicians' Comfort Rating with Prescribing Sildenafil, Methylphenidate, Modafinil, and the Cognitive Enhancer. Male physicians reported being significantly more comfortable prescribing sildenafil (P<0.05); modafinil (P<0.005); and the hypothetical cognitive enhancer (P<0.005), when compared with female physicians. (1.16 MB TIF)

Physician Reasons for Probing or not Probing Cognitive Health in Patients. Table S2 shows the percentage of physicians that selected individual reasons from the list we offered as to why they probe or do not probe cognitive health in patients of different age groups during routine visits. Respondents were able to select as many of the reasons as th...

Physician Comments on being more Comfortable Prescribing Sildenafil Compared to the Other Three Drugs. Physicians were asked to freely respond on why they feel the data showed that the majority of the respondents were significantly more comfortable prescribing sildenafil compared to the other 3 drugs. Their comments were grouped into themes using t...

The ethical dimensions of pharmacological cognitive enhancement have been widely discussed in academic circles and the popular media, but missing from the conversation have been the perspectives of physicians - key decision makers in the adoption of new technologies into medical practice. We queried primary care physicians in major urban centers in...

Rather than recount the societal ills that may arrive with the widespread adoption of cognitive enhancement, it is worth considering the matter in the pragmatic terms that physicians require. To do so, I draw the reader’s attention to a much-ignored issue that bears upon the physician’s decision whether to prescribe a cognitive-enhancement drug—the...

New research reveals the cell mechanisms underlying a meditative state

Neuromarketing is upon us. Companies are springing up to offer their clients brain‐based information about consumer preferences, purporting to bypass focus groups and other marketing research techniques on the premise that directly peering into a consumer's brain while viewing products or brands is a much better predictor of consumer behavior. Thes...

With the use of a novel method for detecting differential gene expression, alterations in functional gene clusters related to transport or oxidative stress response and beta-amyloid (Abeta) peptide metabolism were identified in a HEK293 cell line engineered to overexpress the human ATP binding cassette transporter ABCA2. These included fatty acid b...

Release of acetylcholine within the pontine reticular formation (PRF) from the axon terminals of mesopontine cholinergic neurons has long been hypothesized to play an important role in rapid eye movement (REM) sleep generation. As some of these cholinergic neurons are known to contain substance P (SP), we used anatomical, electrophysiological and p...

A large body of evidence suggests that an increase in the brain beta-amyloid (Abeta) burden contributes to the etiology of Alzheimer's disease (AD). Much is now known about the intracellular processes regulating the production of Abeta, however, less is known regarding its secretion from cells. We now report that p-glycoprotein (p-gp), an ATP-bindi...

A large body of evidence suggests that an increase in the brain β-amyloid (Aβ) burden contributes to the etiology of Alzheimer's disease (AD). Much is now known about the intracellular processes regulating the production of Aβ, however, less is known regarding its secretion from cells. We now report that p-glycoprotein (p-gp), an ATP-binding casset...

The distributions of the type I and type II isoforms of cGMP-dependent protein kinase were determined in the rat brain using immunohistochemistry and in situ hybridization, and compared with the localization of NO synthase determined with NADPH-diaphorase histochemistry. The type I cGMP-dependent protein kinase was highly expressed in the Purkinje...

Although it has long been known that microinjection of the cholinergic agonist carbachol into the medial pontine reticular formation (mPRF) induces a state that resembles rapid eye movement (REM) sleep, it is likely that other transmitters contribute to mPRF regulation of behavioral states. A key candidate is the peptide vasoactive intestinal polyp...

Amyloidogenic processing of the beta-amyloid precursor protein (APP) has been implicated in the pathology of Alzheimer's disease. Because it has been suggested that catabolic processing of the APP holoprotein occurs in acidic intracellular compartments, we studied the effects of the protonophore carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone...

Glutamate is the principal excitatory neurotransmitter in the mammalian brain. Several lines of evidence suggest that glutamatergic hypoactivity exists in the Alzheimer's disease brain, where it may contribute to both brain amyloid burden and cognitive dysfunction. Although metabotropic glutamate receptors have been shown to alter cleavage of the a...

Cholinergic neurons of the laterodorsal tegmental nucleus have been hypothesized to play a critical role in the generation and maintenance of rapid eye movement sleep. Less is known about the function of non-cholinergic laterodorsal tegmental nucleus neurons. As part of our ongoing studies of the brainstem circuitry controlling behavioral state, we...

The properties of postsynaptic potentials evoked by stimulation of cortical, retinal and GABAergic thalamic afferents were examined in vitro in thalamocortical neurons of the guinea-pig dorsal lateral geniculate nucleus. Brief trains of stimulation (2–10 stimuli) delivered to corticothalamic fibers led to a frequency-dependent increase in excitator...

Abstract : Multiple lines of evidence suggest that increased production and/or deposition of the β-amyloid peptide, derived from the amyloid precursor protein, contributes to Alzheimer's disease. A growing list of neuro-transmitters, growth factors, cytokines, and hormones have been shown to regulate amyloid precursor protein processing. Although t...

A variety of methods has been developed based on in vivo microdialysis which allow one to examine the NO/cGMP signal transduction system in action in behaving animals. The extracellular levels of cGMP, the NO oxidative products nitrate and nitrite, and NO itself can all be determined. Using these methods changes in NO and cGMP production in respons...

Nitric oxide (NO) acts via soluble guanylyl cyclase to increase cyclic GMP (cGMP), which can regulate various targets including protein kinases. Western blotting showed that type II cGMP-dependent protein kinase (cGK II) is widely expressed in various brain regions, especially in the thalamus. In thalamic extracts, the phosphorylation of several pr...

Catabolic processing of the amyloid precursor protein (APP) is subject to regulatory control by protein kinases. We hypothesized that this regulation involves sequential activation of the enzymes mitogen-activated protein kinase kinase (MEK) and extracellular signal-regulated protein kinase (ERK). In the present investigation, we provide evidence t...

Since its discovery as a putative neurotransmitter in the CNS, several functional roles have been suggested for nitric oxide (NO). However, few studies have investigated the role of NO in natural physiology. Because NO synthase (NOS) has been localized in regions believed to be important for attention and arousal, we hypothesized that NO production...

Conventional secretory processing of the amyloid precursor protein is nonamyloidogenic, releasing carboxyl-terminus-truncated amyloid precursor protein derivatives while cleaving the amyloid beta-peptide within its sequence. Alternative processing routes are potentially amyloidogenic, yielding the amyloid beta-peptide segment intact. In continuous...

1. The properties of the cholinergic neurons of the rat medial septum and nucleus of the diagonal band of Broca (MS/DBB) were studied using whole cell patch-clamp recordings in an in vitro slice preparation. 2. Both the transmitter phenotype and the intrinsic membrane properties of 56 MS/DBB neurons were determined post hoc by visualizing intracell...

1. Bath application of 10 microM histamine (HA) resulted in a depolarization or inward current in 58/59 cholinergic neurons located in the medial septum and nucleus of the diagonal band of Broca (MS/DBB) in a slice preparation of rat brain. 2. In bridge mode, the histamine-induced depolarization consisted of both fast and slow phases; inward curren...

The reticular activating system is thought to be composed of one or more thalamo-cortical afferents whose activation results in desynchronization of the electroencephalogram. In recent years, a strong body of correlative evidence has accumulated suggesting that mesopontine cholinergic neurons are a key component of the reticular activating system....

Mesopontine cholinergic neurons have long been thought to play a key role in behavioral state control. In particular, they have been implicated in the process of EEG desynchrony and in the generation of rapid eye movement (REM) sleep. However, the behavioral profile of identified mesopontine cholinergic neurons has not been unequivocally demonstrat...

We used voltage-clamp techniques to assess the effects of isoflurane anaesthesia in slices of sensorimotor cortex of guinea pigs and neonatal rats. Isoflurane (0.5-4%) depressed inward Ca(2+)-currents evoked by depolarizing commands from -50 mV. With additional blockade of K(+)-currents by internal Cs+, an early component of the sustained inward cu...

Antihistamines, more formally termed H1 receptor antagonists, are well known to exert sedative effects in humans, yet their locus and mechanism of action in the human brain remains unknown. To better understand this phenomenon, the effects of histamine upon human cortical neurons were studied using intracellular recordings in brain slices maintaine...

Whole cell recording techniques were employed to measure whole cell (Gw) and specific membrane (Gm) conductance in turtle and rat pyramidal neurons in slices. Results indicate that rat neurons are 4.2 times more conductive compared with turtle neurons at 25 degrees C, which is accentuated by temperature, so that rat neurons at 37 degrees C are 22 t...

Inhibition of brainstem cholinergic neurons by noradrenergic neurons of the locus ceruleus has long been suggested as a key mechanism of behavioral state control. In particular, the commonly held view is that noradrenaline (NA) plays a permissive role in rapid eye movement (REM) sleep generation by disinhibiting brainstem cholinergic neurons. While...

1. The whole-cell patch-clamp technique was used to study the membrane properties of identified cholinergic and noncholinergic laterodorsal tegmental neurons in slices of rat brain maintained in vitro. 2. On the basis of their expression of the transient outward potassium current IA and the transient inward calcium current IT, three classes of neur...

The past year has seen some significant advances in our understanding of the structural and functional properties of neuronal voltage-gated Ca2+ channels. Molecular cloning and protein purification studies have identified structural components, and expression studies are beginning to define the biophysical and pharmacological properties of the clon...

Serotonergic suppression of cholinergic neuronal activity implicated in the regulation of rapid eye movement sleep and its associated phenomenon, pontogeniculooccipital waves, has long been postulated, but no direct proof has been available. In this study, intracellular and whole-cell patch-clamp recording techniques were combined with enzyme histo...

1. Intracellular recordings were obtained from histaminergic tuberomammillary (TM) neurons of rat hypothalamus in an in vitro slice preparation. The properties of a time- and voltage-dependent inward current activated on hyperpolarization, Ih, were studied by use of the single-electrode voltage-clamp technique. 2. The activation curve of Ih was wel...

A widespread defense strategy used by hypoxia-tolerant animals is metabolic depression. One possible mechanism for metabolic depression is "channel arrest." This hypothesis predicts that ion leakage through plasma membrane leakage channels is reduced during an anoxic episode. The decreased ion flux would result in the conservation of energy through...