Deep Brain Stimulation for Consciousness Disorders; Technical and Ethical Considerations.

Disorders of Consciousness (DoC) result in profound functional impairment, adversely affecting the lives of a predominantly younger patient population. Currently, effective treatment options for those who have reached chronicity (prolonged symptom duration over 4 weeks) are extremely limited, with the majority of such cases facing life-long dependence on carers and a poor quality of life. Here we briefly review the current evidence on caseload, diagnostic and management options in the United Kingdom (UK), United States of America (USA) and the European Union (EU). We identify key differences as well as similarities in these approaches across respective healthcare systems, highlighting unmet needs in this population. We subsequently present past efforts and the most recent advances in the field of surgical modulation of consciousness through implantable neurostimulation systems. We examine the ethical dilemmas that such a treatment approach may pose, proposing mediating solutions and methodological adjustments to address these concerns. Overall, we argue that there is a strong case for the utilisation of deep brain stimulation (DBS) in the DoC patient cohort. This is based on both promising results of recent clinical trials as well as technological developments. We propose a revitalization of surgical neuromodulation for DoC with a multicenter, multidisciplinary approach and strict monitoring guidelines, in order to not only advance treatment options but also ensure the safeguarding of patients' welfare and dignity.

HRV and EEG correlates of well-being using ultra-short, portable, and low-cost measurements.

Wearable electroencephalography (EEG) and electrocardiography (ECG) devices may offer a non-invasive, user-friendly, and cost-effective approach for assessing well-being (WB) in real-world settings. However, challenges remain in dealing with signal artifacts (such as environmental noise and movements) and identifying robust biomarkers. We evaluated the feasibility of using portable hardware to identify potential EEG and heart-rate variability (HRV) correlates of WB. We collected simultaneous ultrashort (2-min) EEG and ECG data from 60 individuals in real-world settings using a wrist ECG electrode connected to a 4-channel wearable EEG headset. These data were processed, assessed for signal quality, and analyzed using the open-source EEGLAB BrainBeats plugin to extract several theory-driven metrics as potential correlates of WB. Namely, the individual alpha frequency (IAF), frontal and posterior alpha asymmetry, and signal entropy for EEG. SDNN, the low/high frequency (LF/HF) ratio, the Poincaré SD1/SD2 ratio, and signal entropy for HRV. We assessed potential associations between these features and the main WB dimensions (hedonic, eudaimonic, global, physical, and social) implementing a pairwise correlation approach, robust Spearman's correlations, and corrections for multiple comparisons. Only eight files showed poor signal quality and were excluded from the analysis. Eudaimonic (psychological) WB was positively correlated with SDNN and the LF/HF ratio. EEG posterior alpha asymmetry was positively correlated with Physical WB (i.e., sleep and pain levels). No relationships were found with the other metrics, or between EEG and HRV metrics. These physiological metrics enable a quick, objective assessment of well-being in real-world settings using scalable, user-friendly tools.

Emerging paradigms in Alzheimer's therapy.

Alzheimer's disease is a neurodegenerative disorder that affects elderly, and its incidence is continuously increasing across the globe. Unfortunately, despite decades of research, a complete cure for Alzheimer's disease continues to elude us. The current medications are mainly symptomatic and slow the disease progression but do not result in reversal of all disease pathologies. The growing body of knowledge on the factors responsible for the onset and progression of the disease has resulted in the identification of new targets that could be targeted for treatment of Alzheimer's disease. This has opened new vistas for treatment of Alzheimer's disease that have moved away from chemotherapeutic agents modulating a single target to biologics and combinations that acted on multiple targets thereby offering better therapeutic outcomes. This review discusses the emerging directions in therapeutic interventions against Alzheimer's disease highlighting their merits that promise to change the treatment paradigm and challenges that limit their clinical translation.

Neuroplastic Surgery Principles of Computerized Surgical Planning in Complex Cranioplasty Reconstruction.

This article explores the evolution and implementation of three-dimensional (3D) models and Computerized Surgical Planning (CSP) for complex cranioplasty reconstruction and the advances in neuroplastic surgery principles for improved surgical outcomes. Over recent years, CSP has revolutionized the field by employing detailed medical imaging to enhance the accuracy and efficacy of 3D models and for the creation of customized cranial implants (CCIs). The study discusses the advancements of solid alloplastic implants to the future of implants with sophisticated and integrated neurotechnology to treat or enhance patient outcomes. CSP can be used to identify and mitigate complications that can occur within cranioplasty reconstruction and to create CCIs to address the postoperative challenge of temporal hollowing. Despite the promising advancements, the article acknowledges the current limitations of CSP, including cost and technological accessibility, and proposes future directions for research and development. The findings suggest that with further improvements in imaging, biomaterials, and manufacturing techniques, CSP in neuroplastic surgery and other specialties will continue to significantly enhance the precision and personalized care of cranioplasty reconstruction.

Augmented Reality-Guided External Ventricular Drain Placement: A Case Report.

The placement of an external ventricular drain (EVD) is a critical neurosurgical procedure used to relieve intracranial pressure in patients with conditions such as hydrocephalus, traumatic brain injury, and intracranial hemorrhage. Traditional methods rely heavily on anatomical landmarks and the surgeon's experience, which can lead to variability in outcomes and increased risk of complications. Neuronavigation, while available, is infrequently used due to the size, cost, and set-up times associated with these devices. This report explores the use of a headset-based augmented reality (AR) system for guidance during the EVD placement procedure. We describe an AR system that overlays a 3D model of the patient's cranial anatomy, derived from preoperative imaging, onto the patient's head. This system is a head-mounted display and utilizes a rapid fiducial-less registration to provide the surgeon with visualization of 3D anatomy, and targeted trajectories. The system was used with a 32-year-old patient undergoing EVD placement prior to a cranioplasty. Due to the atypical cranial anatomy and due to prior procedures and midline shift, this relatively high-risk catheter placement was an ideal circumstance for the use of AR guidance during the EVD placement. This report described an early use of AR for EVD placement and represents a substantial advancement in neurosurgical practice, offering enhanced precision, efficiency, and safety. Further large-scale studies are warranted to validate these findings and explore the broader applicability of AR in other neurosurgical procedures.

Race-Ethnicity, Rurality, and Age in Prospective Preferences and Concerns Regarding Closed-Loop Implanted Neural Devices.

OBJECTIVE: Responsive and human-centered neurotechnology development requires attention to public perceptions, particularly among groups underserved by existing treatments. METHODS: The authors conducted a preregistered nationally representative survey (https://osf.io/ej9h2) using the NORC at the University of Chicago AmeriSpeak panel. One vignette compared an implanted neural device with surgical resection in a scenario involving epilepsy, and another compared an implanted neural device with medications in a scenario involving mood disorders. The survey also contained questions about respondents' confidence that a device would be available if needed and confidence that enough research has been conducted among people like themselves. Responses were entered into nested survey-weighted logistic regression models, including a base demographic model (to test the overall effect of demographic factors) and an adjusted model that also included socioeconomic, religious and political, and health care access predictors. RESULTS: A total of 1,047 adults responded to the survey, which oversampled Black non-Hispanic (N=214), Hispanic (N=210), and rural (N=219) Americans. In the base demographic model, older Americans were more likely to prefer an implanted device in the two scenarios, and non-Hispanic Black Americans were less likely than non-Hispanic White Americans to prefer a device; rural Americans were less confident than urban or suburban Americans in having access, and non-Hispanic Black and rural Americans were less confident that enough research has been conducted among people like themselves. In adjusted models, income was a key mediator, partially explaining the effect of age and the contrast between Black and White non-Hispanic respondents on preferences for a device in the epilepsy scenario and fully explaining the effect of rurality on confidence in access. CONCLUSIONS: Demographic differences in prospective preferences and concerns highlight the importance of including members of underserved communities in neurotechnology development.

Qualitative studies involving users of clinical neurotechnology: a scoping review.

BACKGROUND: The rise of a new generation of intelligent neuroprostheses, brain-computer interfaces (BCI) and adaptive closed-loop brain stimulation devices hastens the clinical deployment of neurotechnologies to treat neurological and neuropsychiatric disorders. However, it remains unclear how these nascent technologies may impact the subjective experience of their users. To inform this debate, it is crucial to have a solid understanding how more established current technologies already affect their users. In recent years, researchers have used qualitative research methods to explore the subjective experience of individuals who become users of clinical neurotechnology. Yet, a synthesis of these more recent findings focusing on qualitative methods is still lacking. METHODS: To address this gap in the literature, we systematically searched five databases for original research articles that investigated subjective experiences of persons using or receiving neuroprosthetics, BCIs or neuromodulation with qualitative interviews and raised normative questions. RESULTS: 36 research articles were included and analysed using qualitative content analysis. Our findings synthesise the current scientific literature and reveal a pronounced focus on usability and other technical aspects of user experience. In parallel, they highlight a relative neglect of considerations regarding agency, self-perception, personal identity and subjective experience. CONCLUSIONS: Our synthesis of the existing qualitative literature on clinical neurotechnology highlights the need to expand the current methodological focus as to investigate also non-technical aspects of user experience. Given the critical role considerations of agency, self-perception and personal identity play in assessing the ethical and legal significance of these technologies, our findings reveal a critical gap in the existing literature. This review provides a comprehensive synthesis of the current qualitative research landscape on neurotechnology and the limitations thereof. These findings can inform researchers on how to study the subjective experience of neurotechnology users more holistically and build patient-centred neurotechnology.

Enhancing poststroke hand movement recovery: Efficacy of RehabSwift, a personalized brain-computer interface system.

This study explores the efficacy of our novel and personalized brain-computer interface (BCI) therapy, in enhancing hand movement recovery among stroke survivors. Stroke often results in impaired motor function, posing significant challenges in daily activities and leading to considerable societal and economic burdens. Traditional physical and occupational therapies have shown limitations in facilitating satisfactory recovery for many patients. In response, our study investigates the potential of motor imagery-based BCIs (MI-BCIs) as an alternative intervention. In this study, MI-BCIs translate imagined hand movements into actions using a combination of scalp-recorded electrical brain activity and signal processing algorithms. Our prior research on MI-BCIs, which emphasizes the benefits of proprioceptive feedback over traditional visual feedback and the importance of customizing the delay between brain activation and passive hand movement, led to the development of RehabSwift therapy. In this study, we recruited 12 chronic-stage stroke survivors to assess the effectiveness of our solution. The primary outcome measure was the Fugl-Meyer upper extremity (FMA-UE) assessment, complemented by secondary measures including the action research arm test, reaction time, unilateral neglect, spasticity, grip and pinch strength, goal attainment scale, and FMA-UE sensation. Our findings indicate a remarkable improvement in hand movement and a clinically significant reduction in poststroke arm and hand impairment following 18 sessions of neurofeedback training. The effects persisted for at least 4 weeks posttreatment. These results underscore the potential of MI-BCIs, particularly our solution, as a prospective tool in stroke rehabilitation, offering a personalized and adaptable approach to neurofeedback training.

In vivooptogenetics using a Utah Optrode Array with enhanced light output and spatial selectivity.

Objective.Optogenetics allows the manipulation of neural circuitsin vivowith high spatial and temporal precision. However, combining this precision with control over a significant portion of the brain is technologically challenging (especially in larger animal models).Approach.Here, we have developed, optimised, and testedin vivo, the Utah Optrode Array (UOA), an electrically addressable array of optical needles and interstitial sites illuminated by 181µLEDs and used to optogenetically stimulate the brain. The device is specifically designed for non-human primate studies.Main results.Thinning the combinedµLED and needle backplane of the device from 300µm to 230µm improved the efficiency of light delivery to tissue by 80%, allowing lowerµLED drive currents, which improved power management and thermal performance. The spatial selectivity of each site was also improved by integrating an optical interposer to reduce stray light emission. These improvements were achieved using an innovative fabrication method to create an anodically bonded glass/silicon substrate with through-silicon vias etched, forming an optical interposer. Optical modelling was used to demonstrate that the tip structure of the device had a major influence on the illumination pattern. The thermal performance was evaluated through a combination of modelling and experiment, in order to ensure that cortical tissue temperatures did not rise by more than 1 °C. The device was testedin vivoin the visual cortex of macaque expressing ChR2-tdTomato in cortical neurons.Significance.It was shown that the UOA produced the strongest optogenetic response in the region surrounding the needle tips, and that the extent of the optogenetic response matched the predicted illumination profile based on optical modelling-demonstrating the improved spatial selectivity resulting from the optical interposer approach. Furthermore, different needle illumination sites generated different patterns of low-frequency potential activity.

Advancements in brain-computer interfaces for the rehabilitation of unilateral spatial neglect: a concise review.

This short review examines recent advancements in neurotechnologies within the context of managing unilateral spatial neglect (USN), a common condition following stroke. Despite the success of brain-computer interfaces (BCIs) in restoring motor function, there is a notable absence of effective BCI devices for treating cerebral visual impairments, a prevalent consequence of brain lesions that significantly hinders rehabilitation. This review analyzes current non-invasive BCIs and technological solutions dedicated to cognitive rehabilitation, with a focus on visuo-attentional disorders. We emphasize the need for further research into the use of BCIs for managing cognitive impairments and propose a new potential solution for USN rehabilitation, by combining the clinical subtleties of this syndrome with the technological advancements made in the field of neurotechnologies.

Modulation of neuronal dynamics by sustained and activity-dependent continuous-wave near-infrared laser stimulation.

Significance: Near-infrared laser illumination is a non-invasive alternative/complement to classical stimulation methods in neuroscience but the mechanisms underlying its action on neuronal dynamics remain unclear. Most studies deal with high-frequency pulsed protocols and stationary characterizations disregarding the dynamic modulatory effect of sustained and activity-dependent stimulation. The understanding of such modulation and its widespread dissemination can help to develop specific interventions for research applications and treatments for neural disorders. Aim: We quantified the effect of continuous-wave near-infrared (CW-NIR) laser illumination on single neuron dynamics using sustained stimulation and an open-source activity-dependent protocol to identify the biophysical mechanisms underlying this modulation and its time course. Approach: We characterized the effect by simultaneously performing long intracellular recordings of membrane potential while delivering sustained and closed-loop CW-NIR laser stimulation. We used waveform metrics and conductance-based models to assess the role of specific biophysical candidates on the modulation. Results: We show that CW-NIR sustained illumination asymmetrically accelerates action potential dynamics and the spiking rate on single neurons, while closed-loop stimulation unveils its action at different phases of the neuron dynamics. Our model study points out the action of CW-NIR on specific ionic-channels and the key role of temperature on channel properties to explain the modulatory effect. Conclusions: Both sustained and activity-dependent CW-NIR stimulation effectively modulate neuronal dynamics by a combination of biophysical mechanisms. Our open-source protocols can help to disseminate this non-invasive optical stimulation in novel research and clinical applications.

East Asian perspective of responsible research and innovation in neurotechnology.

After more than half a century of research and development (R&D), Brain-computer interface (BCI)-based Neurotechnology continues to progress as one of the leading technologies of the 2020 s worldwide. Various reports and academic literature in Europe and the United States (U.S.) have outlined the trends in the R&D of neurotechnology and the consideration of ethical issues, and the importance of the formulation of ethical principles, guidance and industrial standards as well as the development of relevant human resources has been discussed. However, limited number studies have focused on neurotechnology R&D, the dissemination of neuroethics related to the academic foundation advancing the discussion on ethical principles, guidance and standards or human resource development in the Asian region. This study fills in this gap in understanding of Eastern Asian (China, Korea and Japan) situation based on the participation in activities to develop ethical principles, guidance, and industrial standards for appropriate use of neurotechnology, in addition to literature survey and clinical registries' search investigation reflecting the trends in neurotechnology R&D as well as its social implication in Asian region. The current study compared the results with the situation in Europa and the U.S. and discussed issues that need to be addressed in the future and discussed the significance and potential of corporate consortium initiatives in Japan and examples of ethics and governance activities in Asian Countries.

An Anticipatory Approach to Ethico-Legal Implications of Future Neurotechnology.

This paper provides a justificatory rationale for recommending the inclusion of imagined future use cases in neurotechnology development processes, specifically for legal and policy ends. Including detailed imaginative engagement with future applications of neurotechnology can serve to connect ethical, legal, and policy issues potentially arising from the translation of brain stimulation research to the public consumer domain. Futurist scholars have for some time recommended approaches that merge creative arts with scientific development in order to theorise possible futures toward which current trends in technology development might be steered. Taking a creative, imaginative approach like this in the neurotechnology context can help move development processes beyond considerations of device functioning, safety, and compliance with existing regulation, and into an active engagement with potential future dynamics brought about by the emergence of the neurotechnology itself. Imagined scenarios can engage with potential consumer uses of devices that might come to challenge legal or policy contexts. An anticipatory, creative approach can imagine what such uses might consist in, and what they might imply. Justifying this approach also prompts a co-responsibility perspective for policymaking in technology contexts. Overall, this furnishes a mode of neurotechnology's emergence that can avoid crises of confidence in terms of ethico-legal issues, and promote policy responses balanced between knowledge, values, protected innovation potential, and regulatory safeguards.

Opportunities and obstacles in non-invasive brain stimulation.

Non-invasive brain stimulation (NIBS) is a complex and multifaceted approach to modulating brain activity and holds the potential for broad accessibility. This work discusses the mechanisms of the four distinct approaches to modulating brain activity non-invasively: electrical currents, magnetic fields, light, and ultrasound. We examine the dual stochastic and deterministic nature of brain activity and its implications for NIBS, highlighting the challenges posed by inter-individual variability, nebulous dose-response relationships, potential biases and neuroanatomical heterogeneity. Looking forward, we propose five areas of opportunity for future research: closed-loop stimulation, consistent stimulation of the intended target region, reducing bias, multimodal approaches, and strategies to address low sample sizes.

Ethical Considerations of Neuralink and Brain-Computer Interfaces.

Neuralink is a neurotechnology company founded by Elon Musk in 2016, which has been quietly developing revolutionary technology allowing for ultra-high precision bidirectional communication between external devices and the brain. In this paper, we explore the multifaceted ethical considerations surrounding neural interfaces, analyzing potential societal impacts, risks, and call for a need for responsible innovation. Despite the technological, medical, medicolegal, and ethical challenges ahead, neural interface technology remains extremely promising and has the potential to create a new era of medicine.

Infant neuroscience: how to measure brain activity in the youngest minds.

The functional properties of the infant brain are poorly understood. Recent advances in cognitive neuroscience are opening new avenues for measuring brain activity in human infants. These include novel uses of existing technologies such as electroencephalography (EEG) and magnetoencephalography (MEG), the availability of newer technologies including functional near-infrared spectroscopy (fNIRS) and optically pumped magnetometry (OPM), and innovative applications of functional magnetic resonance imaging (fMRI) in awake infants during cognitive tasks. In this review article we catalog these available non-invasive methods, discuss the challenges and opportunities encountered when applying them to human infants, and highlight the potential they may ultimately hold for advancing our understanding of the youngest minds.

Chilean Supreme Court ruling on the protection of brain activity: neurorights, personal data protection, and neurodata.

This paper discusses a landmark ruling by the Chilean Supreme Court of August 9, 2023 dealing with the right to mental privacy, originated with an action for constitutional protection filed on behalf of Guido Girardi Lavin against Emotiv Inc., a North American company based in San Francisco, California that is commercializing the device "Insight." This wireless device functions as a headset with sensors that collect information about the brain's electrical activity (i.e., neurodata). The discussion revolves around whether neurodata can be considered personal data and whether they could be classified into a special category. The application of the present legislation on data (the most obsolete, such as the Chilean law, and the most recent EU law) does not seem adequate to protect neurodata. The use of neurodata raises ethical and legal concerns that are not fully addressed by current regulations on personal data protection. Despite not being necessarily considered personal data, neurodata represent the most intimate aspects of human personality and should be protected in light of potential new risks. The unique characteristics of neurodata, including their interpretive nature and potential for revealing thoughts and intentions, pose challenges for regulation. Current data protection laws do not differentiate between different types of data based on their informational content, which is relevant for protecting individual rights. The development of new technologies involving neurodata requires particular attention and careful consideration to prevent possible harm to human dignity. The regulation of neurodata must account for their specific characteristics and the potential risks they pose to privacy, confidentiality, and individual rights. The answer lies in the reconfiguration of human rights known as "neurorights" that goes beyond the protection of personal data.

Accelerating neurotechnology development using an Agile methodology.

Novel bioelectronic medical devices that target neural control of visceral organs (e.g., liver, gut, spleen) or inflammatory reflex pathways are innovative class III medical devices like implantable cardiac pacemakers that are lifesaving and life-sustaining medical devices. Bringing innovative neurotechnologies early into the market and the hands of treatment providers would benefit a large population of patients inflicted with autonomic and chronic immune disorders. Medical device manufacturers and software developers widely use the Waterfall methodology to implement design controls through verification and validation. In the Waterfall methodology, after identifying user needs, a functional unit is fabricated following the verification loop (design, build, and verify) and then validated against user needs. Considerable time can lapse in building, verifying, and validating the product because this methodology has limitations for adjusting to unanticipated changes. The time lost in device development can cause significant delays in final production, increase costs, and may even result in the abandonment of the device development. Software developers have successfully implemented an Agile methodology that overcomes these limitations in developing medical software. However, Agile methodology is not routinely used to develop medical devices with implantable hardware because of the increased regulatory burden of the need to conduct animal and human studies. Here, we provide the pros and cons of the Waterfall methodology and make a case for adopting the Agile methodology in developing medical devices with physical components. We utilize a peripheral nerve interface as an example device to illustrate the use of the Agile approach to develop neurotechnologies.