Electrical and Magnetic Neuromodulation Technologies and Brain-Computer Interfaces: Ethical Considerations for Enhancement of Brain Function in Healthy People - A Systematic Scoping Review.

INTRODUCTION: This scoping review aimed to synthesize the fragmented evidence on ethical concerns related to the use of electrical and magnetic neuromodulation technologies, as well as brain-computer interfaces for enhancing brain function in healthy individuals, addressing the gaps in understanding spurred by rapid technological advancements and ongoing ethical debates. METHODS: The following databases and interfaces were queried: MEDLINE (via PubMed), Web of Science, PhilPapers, and Google Scholar. Additional references were identified via bibliographies of included citations. References included experimental studies, reviews, opinion papers, and letters to editors published in peer-reviewed journals that explored the ethical implications of electrical and magnetic neuromodulation technologies and brain-computer interfaces for enhancement of brain function in healthy adult or pediatric populations. RESULTS: A total of 23 articles were included in the review, of which the majority explored expert opinions in the form of qualitative studies or surveys as well as reviews. Two studies explored the view of laypersons on the topic. The majority of evidence pointed to ethical concerns relating to a lack of sufficient efficacy and safety data for these new technologies, with the risks of invasive procedures potentially outweighing the benefits. Additionally, concerns about potential socioeconomic consequences were raised that could further exacerbate existing socioeconomic inequalities, as well as the risk of changes to person and environment. CONCLUSION: This scoping review highlights a critical shortage of ethical research on electrical and magnetic neuromodulation technologies and brain-computer interfaces for enhancement of brain function in healthy individuals, with key concerns regarding the safety, efficacy, and socioeconomic impacts of neuromodulation technologies. It underscores the urgent need for integrating ethical considerations into neuroscientific research to address significant gaps and ensure equitable access and outcomes.

Self-reported neurostimulant use among university students in Santa Maria, Rio Grande do Sul, Brazil.

University students frequently resort to psychostimulants to enhance their physical and mental performance and manage academic pressures. However, these substances can lead to dependence and other undesired symptoms, and little empirical data are available for relevant stakeholders, raising significant concerns in health care. Therefore, this study aims to characterize neurostimulant use among university students in Rio Grande do Sul, Brazil. We collected from 880 students' data using anonymous self-administration. The questionnaire included consumption patterns of caffeine, nicotine, ecstasy, methamphetamine, "merla" (coca base), methylphenidate, cocaine, crack, and ketamine. Additionally, participants shared information on demographic and socioeconomic factors. Use of at least one neurostimulant was reported by89.2% of the participants. Among nonusers, the most frequently cited reason was "previous information about harmful effects of these drugs." Caffeine, followed by nicotine, ecstasy, and methylphenidate were the most consumed substances, with main reasons being "improving academic performance" and "recreation." Women more often consumed caffeine (72.7%), while other psychostimulants were more consumed by men (42.2%) and individuals of other genders (0.5%). Students who consumed other substances had higher family incomes than that of families of caffeine users. In addition, 60.4% of caffeine users resided with family members, whereas 63.3% of users of other substances did not. Our findings can offer essential data on the reasons and symptoms associated with the use of neurostimulants among university students. This information could aid in raising awareness among students, universities, and health-care agencies about this often-neglected subject.

Transcranial direct current stimulation and sporting performance: A systematic review and meta-analysis of transcranial direct current stimulation effects on physical endurance, muscular strength and visuomotor skills.

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that has been linked with a range of physiological and cognitive enhancements relevant to sporting performance. As a number of positive and null findings have been reported in the literature, the present meta-analysis sought to synthesise results across endurance, strength and visuomotor skill domains to investigate if tDCS improves any aspect of sporting performance. Online database searches in August 2020 identified 43 full-text studies which examined the acute effects of tDCS compared to sham/control conditions on physical endurance, muscular strength, and visuomotor skills in healthy adults. Meta-analysis indicated a small overall effect favouring tDCS stimulation over sham/control (standardized mean difference (SMD) = 0.25, CI95%[.14;.36]). Effects on strength (SMD = 0.31, CI95%[.10;.51]) and visuomotor (SMD = 0.29, CI95%[.00;.57]) tasks were larger than endurance performance (SMD = 0.18, CI95%[.00;.37]). Meta-regressions indicated effect sizes were not related to stimulation parameters, but other factors such as genetics, gender, and experience may modulate tDCS effects. The results suggest tDCS has the potential to be used as an ergogenic aid in conjunction with a specified training regime.

Cognitive enhancement: Effects of methylphenidate, modafinil, and caffeine on latent memory and resting state functional connectivity in healthy adults.

Stimulants like methylphenidate, modafinil, and caffeine have repeatedly shown to enhance cognitive processes such as attention and memory. However, brain-functional mechanisms underlying such cognitive enhancing effects of stimulants are still poorly characterized. Here, we utilized behavioral and resting-state fMRI data from a double-blind randomized placebocontrolled study of methylphenidate, modafinil, and caffeine in 48 healthy male adults. The results show that performance in different memory tasks is enhanced, and functional connectivity (FC) specifically between the frontoparietal network (FPN) and default mode network (DMN) is modulated by the stimulants in comparison to placebo. Decreased negative connectivity between right prefrontal and medial parietal but also between medial temporal lobe and visual brain regions predicted stimulant-induced latent memory enhancement. We discuss dopamine's role in attention and memory as well as its ability to modulate FC between large-scale neural networks (e.g., FPN and DMN) as a potential cognitive enhancement mechanism.

How moral neuroenhancement impacts autonomy and agency.

This paper challenges the role individual autonomy has played in debates on moral neuroenhancement (MN). It shows how John Hyman's analysis of agency as consisting of functionally integrated dimensions allows us to reassess the impact of MN on practical agency. I discuss how MN affects what Hyman terms the four dimensions of agency: psychological, ethical, intellectual, and physical. Once we separate the different dimensions of agency, it becomes clear that many authors in the debate conflate the different dimensions in the concept they call 'autonomous agents'. They contend that, for example, reason-giving and previous autonomous acts are relevant to agency as such, when in fact they capture only one aspect of functionally integrated agency. This paper reconsiders MN in light of the functional integration of reason and emotions in practical agency. To illustrate the impact of MN on different aspects of agency, I consider examples from legal practice, which show that autonomy cannot be our sole focus when evaluating the moral implications of MN.

Memory enhancement with stimulants: Differential neural effects of methylphenidate, modafinil, and caffeine. A pilot study.

Human memory is susceptible to manipulation in many respects. While consolidation is well known to be prone to disruption, there is also growing evidence for the enhancement of memory function. Beside cognitive strategies and mnemonic training, the use of stimulants may improve memory processing in healthy adults. In this single-dose, double-blind, within-subject, randomized, placebo-controlled pilot study, 20 mg methylphenidate (N = 13) or 200 mg modafinil (N = 12) or 200 mg caffeine (N = 14) were administrated to in total 39 healthy participants while performing a declarative memory task. Each participant received only one substance and functional magnetic resonance imaging (fMRI) was used to assess drug-dependent memory effects of the substance for encoding and recognition compared to task-related activation under placebo. While methylphenidate showed some behavioral effect regarding memory recall performance, on the neural level, methylphenidate-dependent deactivations were found in fronto-parietal and temporal regions during recognition of previously learned words. No BOLD alterations were seen during encoding. Caffeine led to deactivations in the precentral gyrus during encoding whereas modafinil did not show any BOLD signal alterations at all. These results should be interpreted with caution since this a pilot study with several limitations, most importantly the small number of participants per group. However, our main finding of task-related deactivations may point to a drug-dependent increase of efficiency in physiological response to memory processing.

The polysemy of psychotropic drugs: continuity and overlap between neuroenhancement, treatment, prevention, pain relief, and pleasure-seeking in a clinical setting.

BACKGROUND: Enhancement involves the use of biomedical technologies to improve human capacities beyond therapeutic purposes. It has been well documented that enhancement is sometimes difficult to distinguish from treatment. As a subtype of enhancement, neuroenhancement aims to improve one's cognitive or emotional capacities. MAIN BODY: This article proposes that the notion of neuroenhancement deserves special attention among enhancements in general, because apart from the notion of treatment, it also overlaps with other concepts such as prevention, pain relief, and pleasure seeking. Regarding prevention, patients' mental endurance can be enhanced when a patient is prescribed a selective serotonin reuptake inhibitor for the purpose of preventing the relapse of depression following a stressful situation. As for pain relief, psychiatrists use medication to alleviate distress in patients who experience various types of anxiety; the alleviation of distress is equal to psychological pain relief, but is also an enhancement of the patient's temperamental traits. Regarding pleasure seeking, insidious transition exists between neuroenhancement and pleasure seeking when using psychotropic drugs. It is well known that people use psychostimulants for recreational purposes and to induce overconfidence in one's performance. The polysemy of psychotropics derives from their effects on human sensibility. Therefore, when using psychotropic agents, psychiatrists should pay close attention to what the agent is used for on each patient in each situation, and explicitly share the continuity and overlap in the purpose of prescribing a medication with the patients to make a better clinical decision. CONCLUSIONS: The notion of neuroenhancement overlaps not only with the notion of treatment, but also with other concepts of prevention, pain relief, and pleasure seeking. The continuity between those concepts makes the issues concerning the prescription of psychotropic drugs subtler. Psychiatrists should explicitly share the continuity with the patients to make a better clinical decision.

Enhancing neural efficiency of cognitive processing speed via training and neurostimulation: An fNIRS and TMS study.

Speed of Processing (SoP) represents a fundamental limiting step in cognitive performance which may underlie General Intelligence. The measure of SoP is particularly sensitive to aging, neurological or cognitive diseases, and has become a benchmark for diagnosis, cognitive remediation, and enhancement. Neural efficiency of the Dorsolateral Prefrontal Cortex (DLPFC) is proposed to account for individual differences in SoP. However, the mechanisms by which DLPFC efficiency is shaped by training and whether it can be enhanced remain elusive. To address this, we monitored the brain activity of sixteen healthy participants using functional Near Infrared Spectroscopy (fNIRS) while practicing a common SoP task (Symbol Digit Substitution Task) across 4 sessions. Furthermore, in each session, participants received counterbalanced excitatory repetitive transcranial magnetic stimulation (rTMS) during mid-session breaks. Results indicate a significant involvement of the left-DLPFC in SoP, whose neural efficiency is consistently increased through task practice. Active neurostimulation, but not Sham, significantly enhanced the neural efficiency. These findings suggest a common mechanism by which neurostimulation may aid to accelerate learning.

[Doping for the brain]. / Doping für das Gehirn.

The enhancement of physical and cognitive abilities (i. e. concentration, vigilance, memory) has always been desirable for humans. The term pharmacological neuroenhancement refers to the use of legal or nonprescription psychoactive substances by healthy subjects with the intention of cognitive enhancement. To give the most prominent example, caffeine serves worldwide as a natural stimulant. Brain doping, however, specifies the use of illegal substances or prescription drugs beyond approval with the purpose of cognitive enhancement. Only amphetamines, methylphenidate and modafinil have significant effects on attentiveness, concentration and alertness, whereas other substances, such as anti-dementia drugs or anti-depressants failed to demonstrate cognitive enhancement in healthy subjects.

Effects of Static Magnetic Fields on the Visual Cortex: reversible Visual Deficits and Reduction of Neuronal Activity.

Noninvasive brain stimulation techniques have been successfully used to modulate brain activity, have become a highly useful tool in basic and clinical research and, recently, have attracted increased attention due to their putative use as a method for neuro-enhancement. In this scenario, transcranial static magnetic stimulation (SMS) of moderate strength might represent an affordable, simple, and complementary method to other procedures, such as Transcranial Magnetic Stimulation or direct current stimulation, but its mechanisms and effects are not thoroughly understood. In this study, we show that static magnetic fields applied to visual cortex of awake primates cause reversible deficits in a visual detection task. Complementary experiments in anesthetized cats show that the visual deficits are a consequence of a strong reduction in neural activity. These results demonstrate that SMS is able to effectively modulate neuronal activity and could be considered to be a tool to be used for different purposes ranging from experimental studies to clinical applications.

Sleep Deprivation Impairs and Caffeine Enhances My Performance, but Not Always Our Performance.

What effects do factors that impair or enhance performance in individuals have when these individuals act in groups? We provide a framework, called the GIE ("Effects of Grouping on Impairments and Enhancements") framework, for investigating this question. As prominent examples for individual-level impairments and enhancements, we discuss sleep deprivation and caffeine. Based on previous research, we derive hypotheses on how they influence performance in groups, specifically process gains and losses in motivation, individual capability, and coordination. We conclude that the effect an impairment or enhancement has on individual-level performance is not necessarily mirrored in group performance: grouping can help or hurt. We provide recommendations on how to estimate empirically the effects individual-level performance impairments and enhancements have in groups. By comparing sleep deprivation to stress and caffeine to pharmacological cognitive enhancement, we illustrate that we cannot readily generalize from group results on one impairment or enhancement to another, even if they have similar effects on individual-level performance.

The Art of Living with NZT and ICT: Dialectics of an Artistic Case Study.

I wholeheartedly sympathize conceptually with Coeckelbergh's paper. The dialectical relationship between vulnerability and technology constitutes the core of Hegel's Master and Slave (the primal scene of contemporary philosophy). Yet, the empirical dimension is underdeveloped and Coeckelbergh's ideas could profit from exposure to case studies. Building on a movie/novel (Limitless) devoted to vulnerability coping and living with ICT, I challenge the claim that modern heroism entails overcoming vulnerability with the help of enhancement and computers.

Learning to integrate versus inhibiting information is modulated by age.

Cognitive training aiming at improving learning is often successful, but what exactly underlies the observed improvements and how these differ across the age spectrum are currently unknown. Here we asked whether learning in young and older people may reflect enhanced ability to integrate information required to perform a cognitive task or whether it may instead reflect the ability to inhibit task-irrelevant information for successful task performance. We trained 30 young and 30 aging human participants on a numerosity discrimination task known to engage the parietal cortex and in which cue-integration and inhibitory abilities can be distinguished. We coupled training with parietal, motor, or sham transcranial random noise stimulation, known for modulating neural activity. Numerosity discrimination improved after training and was maintained long term, especially in the training + parietal stimulation group, regardless of age. Despite the quantitatively similar improvement in the two age groups, the content of learning differed remarkably: aging participants improved more in inhibitory abilities, whereas younger subjects improved in cue-integration abilities. Moreover, differences in the content of learning were reflected in different transfer effects to untrained but related abilities: in the younger group, improvements in cue integration paralleled improvements in continuous quantity (time and space), whereas in the elderly group, improvements in numerosity-based inhibitory abilities generalized to other measures of inhibition and corresponded to a decline in space discrimination, possibly because conflicting learning resources are used in numerosity and continuous quantity processing. These results indicate that training can enhance different, age-dependent cognitive processes and highlight the importance of identifying the exact processes underlying learning for effective training programs.

New Developments in Cognitive-Behavioral Therapy for Social Anxiety Disorder.

Social anxiety disorder (SAD) is a highly prevalent and chronic disorder that causes considerable psychosocial impairment. This article reviews recent changes in the definition of SAD in DSM-5 and summarizes the current evidence for effective cognitive-behavioral treatments in adults, children, and adolescents. Current data suggests that cognitive-behavioral therapy (CBT) is efficacious in the treatment of this condition. Among different CBT approaches, individual cognitive therapy may be associated with the largest effect sizes. In this review, interventions targeting dysfunctional cognitive processes that contribute to the effective treatment of SAD are discussed. Some recent findings from neuroimaging research and studies on the augmentation of CBT using neuroenhancers indicate that changes in emotion regulation as well as fear extinction are important psychological mediators of positive outcome. Furthermore, internet-delivered CBT is a promising field of technological innovation that may improve access to effective treatments. Despite the availability of effective treatments, treatment-resistant SAD remains a common problem in clinical practice that requires more research efforts. Finally, potential areas for further development of CBT as well as its dissemination in health care are summarized.

Intention and Moral Enhancement.

Recently philosophers have proposed a wide variety of interventions referred to as 'moral enhancements'. Some of these interventions are concerned with helping individuals make more informed decisions; others, however, are designed to compel people to act as the intervener sees fit. Somewhere between these two extremes lie interventions designed to direct an agent's attention either towards morally relevant issues - hat-hanging - or away from temptations to do wrong - hat-hiding. I argue that these interventions fail to constitute genuine moral enhancement because, although they may result in more desirable outcomes - more altruism, more law-following, and/or less self-destructive behavior, they ignore a person's intentions, and often what makes an action right or wrong is the intent behind it.

Shaping memory accuracy by left prefrontal transcranial direct current stimulation.

Human memory is dynamic and flexible but is also susceptible to distortions arising from adaptive as well as pathological processes. Both accurate and false memory formation require executive control that is critically mediated by the left prefrontal cortex (PFC). Transcranial direct current stimulation (tDCS) enables noninvasive modulation of cortical activity and associated behavior. The present study reports that tDCS applied to the left dorsolateral PFC (dlPFC) shaped accuracy of episodic memory via polaritiy-specific modulation of false recognition. When applied during encoding of pictures, anodal tDCS increased whereas cathodal stimulation reduced the number of false alarms to lure pictures in subsequent recognition memory testing. These data suggest that the enhancement of excitability in the dlPFC by anodal tDCS can be associated with blurred detail memory. In contrast, activity-reducing cathodal tDCS apparently acted as a noise filter inhibiting the development of imprecise memory traces and reducing the false memory rate. Consistently, the largest effect was found in the most active condition (i.e., for stimuli cued to be remembered). This first evidence for a polarity-specific, activity-dependent effect of tDCS on false memory opens new vistas for the understanding and potential treatment of disturbed memory control.

The medicalization of love.

Pharmaceuticals or other emerging technologies could be used to enhance (or diminish) feelings of lust, attraction, and attachment in adult romantic partnerships. Although such interventions could conceivably be used to promote individual (and couple) well-being, their widespread development and/or adoption might lead to the 'medicalization' of human love and heartache--for some, a source of a serious concern. In this essay, we argue that the medicalization of love need not necessarily be problematic, on balance, but could plausibly be expected to have either good or bad consequences depending upon how it unfolds. By anticipating some of the specific ways in which these technologies could yield unwanted outcomes, bioethicists and others can help to direct the course of love's medicalization--should it happen to occur--more toward the 'good' side than the 'bad.'

Battery powered thought: enhancement of attention, learning, and memory in healthy adults using transcranial direct current stimulation.

This article reviews studies demonstrating enhancement with transcranial direct current stimulation (tDCS) of attention, learning, and memory processes in healthy adults. Given that these are fundamental cognitive functions, they may also mediate stimulation effects on other higher-order processes such as decision-making and problem solving. Although tDCS research is still young, there have been a variety of methods used and cognitive processes tested. While these different methods have resulted in seemingly contradictory results among studies, many consistent and noteworthy effects of tDCS on attention, learning, and memory have been reported. The literature suggests that although tDCS as typically applied may not be as useful for localization of function in the brain as some other methods of brain stimulation, tDCS may be particularly well-suited for practical applications involving the enhancement of attention, learning, and memory, in both healthy subjects and in clinical populations.

Transcranial cerebellar direct current stimulation (tcDCS): motor control, cognition, learning and emotions.

The neurological manifestations of cerebellar diseases range from motor to cognitive or behavioral abnormalities. Experimental data in healthy subjects extend the cerebellar role to learning, emotional and mood control. The need for a non-invasive tool to influence cerebellar function in normal and pathological conditions led researchers to develop transcranial cerebellar direct current stimulation (tcDCS). tcDCS, like tDCS, depends on the principle that weak direct currents delivered at around 2mA for minutes over the cerebellum through surface electrodes induce prolonged changes in cerebellar function. tcDCS modulates several cerebellar skills in humans including motor control, learning and emotional processing. tcDCS also influences the cerebello-brain interactions induced by transcranial magnetic stimulation (TMS), walking adaptation, working memory and emotional recognition. Hence tcDCS is a simple physiological tool that can improve our physiological understanding of the human cerebellum, and should prove useful also in patients with cerebellar dysfunction or psychiatric disorders and those undergoing neurorehabilitation to enhance neuroplasticity.