Many experimental brain-computer interfaces (BCIs) are currently being medically tested in paralyzed patients. While the new generations of implantable BCIs move rapidly ahead at trying to increase the patients’ well-being, ethical concerns about their potential effects on patients’ psychological dimensions (e.g. sense of agency and control) are growing. An important ethical concern to explore is how BCIs may introduce unprecedented vulnerabilities to implanted individuals.Our chapter shows that, on the one hand, BCIs can empower the sense of self and control, (...) which contribute to well-being. On the other hand, they can introduce unprecedented vulnerabilities, for example, by inducing radical distress, feelings of loss of control, and a rupture of patient identity, which decrease one’s well-being. To investigate a possible solution to this problem we propose to understand the implementation of a BCI system in one’s body through the capability approach. This calls for a careful ethical examination of new morally salient issues prior to seeing an increase in BCI-related psychological effects in an open market. (shrink)

Revolutions in semiconductor device miniaturization, bioelectronics, and applied neural control technologies are enabling scientists to create machine-assisted minds, science fiction's “cyborgs.” In a paper published in 1999, we sought to draw attention to the advances in prosthetic devices, to the myriad of artificial implants, and to the early developments of this technology in cochlear and retinal implants. Our concern, then and now, was to draw attention to the ethical issues arising from these innovations. Since that time, breakthroughs have occurred at (...) a breathtaking pace. Scientists, researchers, and engineers using differing methodologies are pursuing the possibilities of direct interfaces between brains and machines. Technological innovations as such are neither good nor evil; it is the uses devised for them that create moral implications. As there can be ethical problems inherent in the proper human uses of technologies and because brain chips are a very likely future technology, it is prudent to formulate policies and regulations that will mitigate their ill effects before the technologies are widespread. Unlike genetic technologies, which have received widespread scrutiny within the scientific community, national governments, and international forums, brain–machine interfaces have received little social or ethical scrutiny. However, the potential of this technology to change and significantly affect humans is potentially far greater than that of genetic enhancements, because genetic enhancements are inherently limited by biology and the single location of an individual, whereas hybrids of human and machine are not so restricted. Today, intense interest is focused on the development of drugs to enhance memory; yet, these drugs merely promise an improvement of normal memory, not the encyclopedic recall of a computer-enhanced mind combined with the ability to share information at a distance. The potential of brain chips for transforming humanity are astounding. This paper describes advances in hybrid brain–machine interfaces, offers some likely hypotheses concerning future developments, reflects on the implications of combining cloning and transplanted brain chips, and suggests some potential methods of regulating these technologies. (shrink)

Biomedical engineering technologies such as brain–machine interfaces and neuroprosthetics are advancements which assist human beings in varied ways. There are exciting yet speculative visions of how the neurosciences and bioengineering may influence human nature. However, these could be preparing a possible pathway towards an enhanced and even posthuman future. This article seeks to investigate several ethical themes and wider questions of enhancement, transhumanism and posthumanism. Four themes of interest are: autonomy, identity, futures, and community. Three larger questions (...) can be asked: will everyone be enhanced? Will we be “human” if we are not, one day, transhuman? Should we be enhanced or not? The article proceeds by concentrating on a widespread and sometimes controversial application: the cochlear implant, an auditory prosthesis implanted into Deaf patients. Cochlear implantation and its reception in both the deaf and hearing communities have a distinctive moral discourse, which can offer surprising insights. The paper begins with several points about the enhancement of human beings, transhumanism’s reach beyond the human, and posthuman aspirations. Next it focuses on cochlear implants on two sides. Firstly, a shorter consideration of what technologies may do to humans in a transhumanist world. Secondly, a deeper analysis of cochlear implantation’s unique socio-political movement, its ethical explanations and cultural experiences linked with pediatric cochlear implantation—and how those wary of being thrust towards posthumanism could marshal such ideas by analogy. As transhumanism approaches, the issues and questions merit continuing intense analysis. (shrink)

Cerebral organoid models in-of-themselves are considered as an alternative to research animal models. But their developmental and biological limitations currently inhibit the probability that organoids can fully replace animal models. Furthermore, these organoid limitations have, somewhat ironically, brought researchers back to the animal model via xenotransplantation, thus creating hybrids and chimeras. In addition to attempting to study and overcome cerebral organoid limitations, transplanting cerebral organoids into animal models brings an opportunity to observe behavioral changes in the animal itself. Traditional animal (...) ethics frameworks, such as the well-known three Rs (reduce, refine, and replace), have previously addressed chimeras and xenotransplantation of tissue. But these frameworks have yet to completely assess the neural-chimeric possibilities. And while the three Rs framework was a historical landmark in animal ethics, there are identifiable gaps in the framework that require attention. The authors propose to utilize an expanded three Rs framework initially developed by David DeGrazia and Tom L. Beauchamp, known as the Six Principles (6Ps). This framework aims to expand upon the three Rs, fill in the gaps, and be a practical means for assessing animal ethical issues like that of neural-chimeras and cerebral organoid xenotransplantation. The scope of this 6Ps application will focus on two separate but recent studies, which were published in 2019 and 2020. First, they consider a study wherein cerebral organoids were grown from donors with Down syndrome and from neurotypical donors. After these organoids were grown and studied, they were then surgically implanted into mouse models to observe the physiological effects and any behavioral change in the chimera. Second, they consider a separate study wherein neurotypical human embryonic stem cell-derived cerebral organoids were grown and transplanted into mouse and macaque models. The aim was to observe if such a transplantation method would contribute to therapies for brain injury or stroke. The authors place both studies under the lens of the 6Ps framework, assess the relevant contexts of each case, and provide relevant normative conclusions. In this way, they demonstrate how the 6Ps could be applied in future cases of neural-chimeras and cerebral organoid xenotransplantation. (shrink)

Cranial electrical stimulation has been applied at various current levels in both adults and children with neurological conditions with seemingly promising but somewhat inconsistent results. Stimulation-induced spatial electric fields within a specific brain region are likely a significant contributing factor for the biological effects. Although several simulation models have been used to predict EF distributions in the brain, these models actually have not been validated by in vivo CES-induced EF measurements in the live human brain. This (...) study directly measured the CES-induced voltage changes with implanted stereotactic-electroencephalographic electrodes in twenty-one epilepsy participants and then compared these measured values with the simulated ones obtained from the personalized models. In addition, we further investigated the influence of stimulation frequency, intensity, electrode montage and age on EFs in parts of participants. We found both measured voltages and EFs obtained in vivo are highly correlated with the predicted ones in our cohort. In white matter and gray matter, the measured voltages linearly increased when the stimulation intensity increased from 5 to 500 μA but showed no significant changes with changing stimulation frequency from 0.5 to 200 Hz. Electrode montage, but not age, significantly affects the distribution of the EFs. Our in vivo measurements demonstrate that the individualized simulation model can reliably predict the CES-induced EFs in both adults and children. It also confirms that the CES-induced EFs highly depend on the electrode montages and individual anatomical features. (shrink)

The paper focuses on processes of normalization through which dis/ability is simultaneously produced in specific collectives, networks, and socio-technological systems that enable the construction of such demarcations. Our point of departure is the cochlear implant, a neuroprosthetic device intended to replace and/or augment the function of the damaged inner ear. Unlike hearing aids, which amplify sounds, the CI does the work of damaged hair cells in the inner ear by providing sound signals to the brain. We examine the processes (...) of the CI’s genesis as well as its specific uses by and interrelations to the different and divergent actors that the CI assembles. We argue that the technological device and the implicated normalization process mobilize complex effects in varying socio-technical arrangements. The CI is conceived as a “boundary object” [89] or a “quasi-object” [49, 83], i.e., a metastabilized medium of translation that coordinates social, cultural, and technological action. Although intended to transform non-hearing or hard of hearing people into competent and “normal” hearing subjects, the CI system reproduces the asymmetrical structures of the disability discourse [14] through its function of “developing and maintaining coherence between intersecting social worlds” [89, 393]. Additionally, it initiates controversial discourses that have resulted in new forms of biosocial collectivities ranging from cochlear implantees with normal human hearing to human configurations who have passed through human enhancement. Our approach is thus situated at the intersection of disability and media studies and tackles the particular conditions technological media configurations impose upon the production of dis/ability. (shrink)

Deep Brain Stimulation (DBS) is a treatment involving the implantation of electrodes into the brain. Presently, it is used for neurological disorders like Parkinson’s disease, but indications are expanding to psychiatric disorders such as depression, addiction and Obsessive Compulsive Disorder (OCD). Theoretically, it may be possible to use DBS for the enhancement of various mental functions. This article discusses a case of an OCD patient who felt very happy with the DBS treatment, even though her symptoms were (...) not reduced. First, it is explored if the argument that ‘doctors are not in the business of trading happiness’, as used by her psychiatrist to justify his discontinuation of the DBS treatment, holds. The relationship between enhancement and the goals of medicine is discussed and it is concluded that even though the goals of medicine do not set strict limits and may even include certain types of enhancement, there are some good reasons for limiting the kind of things doctors are required or allowed to do. Next, the case is discussed from the perspective of beneficence and autonomy. It is argued that making people feel good is not the same as enhancing their well-being and that it is unlikely—though not absolutely impossible—that the well-being of the happy OCD patient is really improved. Finally, some concerns regarding the autonomy of a request made under the influence of DBS treatment are considered. (shrink)

Recording and manipulating neuronal ensemble activity is a key requirement in advanced neuromodulatory and behavior studies. Devices capable of both recording and manipulating neuronal activity brain-computer interfaces should ideally operate un-tethered and allow chronic longitudinal manipulations in the freely moving animal. In this study, we designed a new intracortical BCI feasible of telemetric recording and stimulating local gray and white matter of visual neural circuit after irradiation exposure. To increase the translational reliance, we put forward a Göttingen minipig model. (...) The animal was stereotactically irradiated at the level of the visual cortex upon defining the target by a fused cerebral MRI and CT scan. A fully implantable neural telemetry system consisting of a 64 channel intracortical multielectrode array, a telemetry capsule, and an inductive rechargeable battery was then implanted into the visual cortex to record and manipulate local field potentials, and multi-unit activity. We achieved a 3-month stability of the functionality of the un-tethered BCI in terms of telemetric radio-communication, inductive battery charging, and device biocompatibility for 3 months. Finally, we could reliably record the local signature of sub- and suprathreshold neuronal activity in the visual cortex with high bandwidth without complications. The ability to wireless induction charging combined with the entirely implantable design, the rather high recording bandwidth, and the ability to record and stimulate simultaneously put forward a wireless BCI capable of long-term un-tethered real-time communication for causal preclinical circuit-based closed-loop interventions. (shrink)

Patients requiring deep brain stimulation due to intracerebral metallic foreign substances have not been reported elsewhere in the world. Additionally, the long-term effects of metallic foreign bodies on deep brain stimulation are unknown. A 79-year-old man with a 5-year history of Parkinson's disease reported that, 40 years ago, while playing with a pistol, a metallic bullet was accidentally discharged into the left brain through the edge of the left eye, causing no discomfort other than blurry vision in (...) the left eye. DBS was performed due to the short duration of efficacy for oral medication. Because the bullet was on the left subthalamic nucleus electrode trajectory and the patient's right limb was primarily stiff, the patient received globus pallidus interna -DBS implantation in the left hemisphere and STN-DBS implantation in the right hemisphere. During a 6-month postoperative follow-up, the patient's PD symptoms were effectively managed with no noticeable discomfort. (shrink)

Single units that are not related to the desired task can become related to the task by conditioning their firing rates. We theorized that, during conditioning of firing rates to a tone, (a) unrelated single units would be recruited to the task; (b) the recruitment would depend on the phase of the task; (c) tones of different frequencies would produce different patterns of single unit recruitment. In our mute locked-in participant, we conditioned single units using tones of different frequencies emitted (...) from a tone generator. The conditioning task had three phases: Listen to the tone for 20 s, then silently sing the tone for 10 s, with a prior control period of resting for 10 s. Twenty single units were recorded simultaneously while feedback of one of the twenty single units was made audible to the mute locked-in participant. The results indicate that (a) some of the non-audible single units were recruited during conditioning, (b) some were recruited differentially depending on the phase of the paradigm (listen, rest, or silent sing), and (c) single unit firing patterns were specific for different tone frequencies such that the tone could be recognized from the pattern of single unit firings. These data are important when conditioning single unit firings in brain-computer interfacing tasks because they provide evidence that increased numbers of previously unrelated single units can be incorporated into the task. This incorporation expands the bandwidth of the recorded single unit population and thus enhances the brain-computer interface. This is the first report of conditioning of single unit firings in a human participant with a brain to computer implant. (shrink)

In a world surrounded by smart objects from sensors to automated medical devices, the ubiquity of ‘smart’ seems matched only by its lack of clarity. In this article, we use our discussions with expert stakeholders working in areas of implantable medical devices such as cochlear implants, implantable cardiac defibrillators, deep brain stimulators and in vivo biosensors to interrogate the difference facets of smart in ‘implantable smart technologies’, considering also whether regulation needs to respond to the autonomy that such artefacts (...) carry within them. We discover that when smart technology is deconstructed it is a slippery and multi-layered concept. A device’s ability to sense and transmit data and automate medicine can be associated with the ‘sting’ of autonomy being disassociated from human control as well as affecting individual, group, and social environments. (shrink)

The loss or absence of vision is probably one of the most incapacitating events that can befall a human being. The importance of vision for humans is also reflected in brain anatomy as approximately one third of the human brain is devoted to vision. It is therefore unsurprising that throughout history many attempts have been undertaken to develop devices aiming at substituting for a missing visual capacity. In this review, we present two concepts that have been (...) prevalent over the last two decades. The first concept is sensory substitution, which refers to the use of another sensory modality to perform a task that is normally primarily sub-served by the lost sense. The second concept is cross-modal plasticity, which occurs when loss of input in one sensory modality leads to reorganization in brain representation of other sensory modalities. Both phenomena are training-dependent. We also briefly describe the history of blindness from ancient times to modernity, and then proceed to address themeansthat have been used to help blind individuals, with an emphasis on modern technologies, invasive (various type of surgical implants) and non-invasive devices. With the advent of brain imaging, it has become possible to peer into the neural substrates of sensory substitution and highlight the magnitude of the plastic processes that lead to a rewired brain. Finally, we will address the important question of the value and practicality of the available technologies and future directions. (shrink)

"Cet essai de bioéthique propose de penser l'Homme et son avenir à travers une innovation technologique extraordinaire : les implants cérébraux. Utilisés déjà dans des contextes de maladies, leur développement actuel laisse espérer pouvoir contrôler bientôt des dispositifs robotiques en connectant le cerveau à des ordinateurs équipés d'intelligences artificielles. Si les premiers résultats sont très encourageants, ces interfaces cerveau-machines posent néanmoins un questionnement éthique majeur. Que devient l'Homme si son cerveau fonctionne avec un dispositif électronique "intelligent" implanté? Pourrait-on percer les (...) secrets de ses pensées? Pourrait-on augmenter son intelligence ou sa mémoire? Afin d'appréhender ces trois questions, cet essai commence par penser l'Homme et son rapport aux technologies : la vulnérabilité humaine n'appelle-t-elle pas le recours aux techniques et technologies pour habiter le monde? Pour aider certaines personnes en situation de handicap, n'a-t-on pas besoin parfois de dépasser techniquement les limites de la nature humaine? Mais peut-on pour autant tout se permettre, même pour compenser un handicap? Comment accompagner les chercheurs dans leur propre questionnement? Ne serait-ce qu'une question de bon et de mauvais usage des techniques et technologies? C'est cette aventure philosophique et bioéthique que propose cet essai.". (shrink)

In a world surrounded by smart objects from sensors to automated medical devices, the ubiquity of ‘smart’ seems matched only by its lack of clarity. In this article, we use our discussions with expert stakeholders working in areas of implantable medical devices such as cochlear implants, implantable cardiac defibrillators, deep brain stimulators and in vivo biosensors to interrogate the difference facets of smart in ‘implantable smart technologies’, considering also whether regulation needs to respond to the autonomy that such artefacts (...) carry within them. We discover that when smart technology is deconstructed it is a slippery and multi-layered concept. A device’s ability to sense and transmit data and automate medicine can be associated with the ‘sting’ of autonomy being disassociated from human control as well as affecting individual, group, and social environments. (shrink)

Enhancing brain activity and function is a very ancient practice which is usually accomplished by taking illegal drugs. Prescription medication is becoming more commonly used as a means of enhancing mood, and recently, it has become possible to modulate mood by applying magnetic or electrical current to the brain or by training the brain to work at predetermined oscillations. A summary of the available neuromodulation techniques will be presented associated with data from human subjects implanted with (...) cortical and/or subcutaneous electrodes that demonstrate the potential for electrical neuro-enhancement. (shrink)

'Brainjacking’ refers to the exercise of unauthorized control of another’s electronic brain implant. Whilst the possibility of hacking a Brain–Computer Interface (BCI) has already been proven in both experimental and real-life settings, there is reason to believe that it will soon be possible to interfere with the software settings of the Implanted Pulse Generators (IPGs) that play a central role in Deep Brain Stimulation (DBS) systems. Whilst brainjacking raises ethical concerns pertaining to privacy and physical or psychological (...) harm, we claim that the possibility of brainjacking DBS raises particularly profound concerns about individual autonomy, since the possibility of hacking such devices raises the prospect of third parties exerting influence over the neural circuits underpinning the subject’s cognitive, emotional and motivational states. However, although it seems natural to assume that brainjacking represents a profound threat to individual autonomy, we suggest that the implications of brainjacking for individual autonomy are complicated by the fact that technologies targeted by brainjacking often serve to enhance certain aspects of the user’s autonomy. The difficulty of ascertaining the implications of brainjacking DBS for individual autonomy is exacerbated by the varied understandings of autonomy in the neuroethical and philosophical literature. In this paper, we seek to bring some conceptual clarity to this area by mapping out some of the prominent views concerning the different dimension of autonomous agency, and the implications of brainjacking DBS for each dimension. Drawing on three hypothetical case studies, we show that there could plausibly be some circumstances in which brainjacking could potentially be carried out in ways that could serve to enhance certain dimensions of the target’s autonomy. Our analysis raises further questions about the power, scope, and necessity of obtaining prior consent in seeking to protect patient autonomy when directly interfering with their neural states, in particular in the context of self-regulating closed-loop stimulation devices. (shrink)

Brain-machine interfaces are a growing field of research and application. The increasing possibilities to connect the human brain to electronic devices and computer software can be put to use in medicine, the military, and entertainment. Concrete technologies include cochlear implants, Deep Brain Stimulation, neurofeedback and neuroprosthesis. The expectations for the near and further future are high, though it is difficult to separate hope from hype. The focus in this paper is on the effects that these new (...) technologies may have on our ‘symbolic order’—on the ways in which popular categories and concepts may change or be reinterpreted. First, the blurring distinction between man and machine and the idea of the cyborg are discussed. It is argued that the morally relevant difference is that between persons and non-persons, which does not necessarily coincide with the distinction between man and machine. The concept of the person remains useful. It may, however, become more difficult to assess the limits of the human body. Next, the distinction between body and mind is discussed. The mind is increasingly seen as a function of the brain, and thus understood in bodily and mechanical terms. This raises questions concerning concepts of free will and moral responsibility that may have far reaching consequences in the field of law, where some have argued for a revision of our criminal justice system, from retributivist to consequentialist. Even without such a (unlikely and unwarranted) revision occurring, brain-machine interactions raise many interesting questions regarding distribution and attribution of responsibility. (shrink)

In a world surrounded by smart objects from sensors to automated medical devices, the ubiquity of ‘smart’ seems matched only by its lack of clarity. In this article, we use our discussions with expert stakeholders working in areas of implantable medical devices such as cochlear implants, implantable cardiac defibrillators, deep brain stimulators and in vivo biosensors to interrogate the difference facets of smart in ‘implantable smart technologies’, considering also whether regulation needs to respond to the autonomy that such artefacts (...) carry within them. We discover that when smart technology is deconstructed it is a slippery and multi-layered concept. A device’s ability to sense and transmit data and automate medicine can be associated with the ‘sting’ of autonomy being disassociated from human control as well as affecting individual, group, and social environments. (shrink)

Closed Loop medical devices such as Closed Loop Deep Brain Stimulation and Brain Computer Interface are some of the emerging neurotechnologies. New generations of implantable brain–computer interfaces have recently gained success in human clinical trials. These implants detect specific neuronal patterns and provide the subject with information to respond to these patterns. Further, Closed Loop brain devices give control to the subject so that he can respond and decide on a therapeutic goal. Although the implants (...) have improved subjects’ quality of life, their use has raised varied ethical concerns. The aim of this study is to provide an overview of the ethical implications specific to the therapeutic goals of closed loop brain implants. The authors analyze the related work qualitatively and quantitatively so as to help readers in understanding the various ethical implications of closed loop brain implants. (shrink)

In the following text, medical, anthropological and ethical issues of deep brain stimulation, a medical technology in which electrodes implanted in the human brain electrically influence specified brain regions, will be discussed. After a brief account of the deep brain stimulation procedure and its chances and risks, anthropological and ethical aspects of the approach will be discussed. These relate to the reversibility of the procedure and to the patient’s capacity to control the effects it exerts (...) in the brain, to modifications and fluctuations in a person’s character traits and individuality brought about by neurostimulation, and to the range of legitimate, adequate uses of the deep brain stimulation approach. The paper concludes that deep brain stimulation should be confined to therapeutic contexts and to severe, otherwise treatment-refractory disorders in which the aim is to normalize brain functioning. Apart from this, it should not be used to modify a person’s individual character traits and behaviour or to enhance human traits. (shrink)

Deep Brain Stimulation (DBS) is an invasive therapeutic method involving the implantation of electrodes and the electrical stimulation of specific areas of the brain to modulate their activity. DBS brings therapeutic benefits, but can also have adverse side effects. Recently, neuroethicists have recognized that DBS poses a threat to the very fabric of human existence, namely, to the selves of patients. This article provides a review of the neuroethical literature examining this issue, and identifies the crucial (...) dimensions related to the self which DBS may endanger—personal identity, authenticity, and autonomy. The most influential theories accounting for these dimensions are analyzed herein, and it is argued that most of these theories require further refinement. This paper also demonstrates the interrelation between personal identity, authenticity, and autonomy, and concludes that one can only fully understand the impact of DBS on the self when all of these factors are taken into account. (shrink)

This article provides an ethnographic account of pediatric cochlear implantation, revealing an important shift in the definition of deafness from a sensory loss to a neurological processing problem. In clinical and long-term therapeutic practices involved in pediatric implantation, the cochlear implant is recast as a device that merely provides access to the brain. The “real” treatment emerges as long-term therapeutic endeavors focused on neurological training. This redefinition then ushers in an ensuing responsibility to “train the brain,” (...) subsequently displacing failure from the device onto the individual’s ability to train his or her brain. New caregiving techniques that accompany implantation are understood through neuropolitics, showing how parents are encouraged to engage in neuro-self-governance, and how the concept of neuroplasticity is used to cultural ends. (shrink)

People suffering from Obsessive-Compulsive Disorder (OCD) do things they do not want to do, and/or they think things they do not want to think. In about 10 percent of OCD patients, none of the available treatment options is effective. A small group of these patients is currently being treated with deep brain stimulation (DBS). Deep brain stimulation involves the implantation of electrodes in the brain. These electrodes give a continuous electrical pulse to the brain area (...) in which they are implanted. It turns out that patients may experience profound changes as a result of DBS treatment. It is not just the symptoms that change; patients rather seem to experience a different way of being in the world. These global effects are insufficiently captured by traditional psychiatric scales, which mainly consist of behavioural measures of the severity of the symptoms. In this article we aim to capture the changes in the patients’ phenomenology and make sense of the broad range of changes they report. For that we introduce an enactive, affordance-based model that fleshes out the dynamic interactions between person and world in four aspects. The first aspect is the patients’ experience of the world. We propose to specify the patients’ world in terms of a field of affordances, with the three dimensions of broadness of scope (‘width’ of the field), temporal horizon (‘depth’), and relevance of the perceived affordances (‘height’). The second aspect is the person-side of the interaction, that is, the patients’ self-experience, notably their moods and feelings. Thirdly, we point to the different characteristics of the way in which patients relate to the world. And lastly, the existential stance refers to the stance that patients take towards the changes they experience: the second-order evaluative relation to their interactions and themselves. With our model we intend to specify the notion of being in the world in order to do justice to the phenomenological effects of DBS treatment. (shrink)

IntroductionDeep brain stimulation (DBS) is increasingly used to treat the symptoms of various neurologic and psychiatric conditions. People can undergo the procedure during reproductive years but the safety of DBS in pregnancy remains relatively unknown given the paucity of published cases. We thus conducted a review of the literature to determine the state of current knowledge about DBS in pregnancy and to determine how eligibility criteria are approached in clinical trials with respect to pregnancy and the potential for pregnancy.MethodsA (...) literature review was conducted in EMBASE to identify articles involving DBS and pregnancy. Two reviewers independently analyzed the articles to confirm inclusion. Data extracted for analysis included conditions treated, complications at all stages of pregnancy, neonatal/pediatric outcomes, and DBS target. A second search was then conducted using www.clinicaltrials.gov. The same two reviewers then assessed whether each trial excluded pregnant individuals, lactating individuals, or persons of childbearing age planning to conceive. Also assessed was whether contraception had to be deemed adequate prior to enrollment.ResultsThe literature search returned 681 articles. Following independent analysis and agreement of two reviewers, 8 pregnancy related DBS articles were included for analysis. These articles described 27 subjects, 29 pregnancies (2 with subsequent pregnancies), and 31 infants (2 twin pregnancies). There was 1 preterm birth at 35 weeks, and 3 patients who experienced discomfort from the DBS battery (i.e., impulse generator) placement site. All 27 patients had a DBS device implanted before they became pregnant, which remained in use throughout their pregnancy. There was exclusion of pregnant individuals from 68% of 135 interventional trials involving DBS. Approximately 44% of these trials excluded persons of childbearing age not on “adequate contraception” or wishing to conceive in the coming years. Finally, 22% excluded breastfeeding persons.ConclusionThe data from 29 pregnancies receiving DBS treatment during pregnancy was not associated with unexpected pregnancy or post-partum complication patterns. Many clinical trials have excluded pregnant individuals. Documentation of outcomes in larger numbers of pregnancies will help clarify the safety profile and will help guide study designs that will safely include pregnant patients. (shrink)

Neural engineering technologies such as implanted deep brain stimulators and brain-computer interfaces represent exciting and potentially transformative tools for improving human health and well-being. Yet their current use and future prospects raise a variety of ethical and philosophical concerns. Devices that alter brain function invite us to think deeply about a range of ethical concerns—identity, normality, authority, responsibility, privacy, and justice. If a device is stimulating my brain while I decide upon an action, am I (...) still the author of the action? Does a device make the interiority of my experience accessible to others? Will the device change the way I think of myself and others think of me? Such fundamental questions arise even when a device is designed for only a relatively circumscribed purpose, such as restoring functioning via a smart prosthetic. We are part of a National Science Foundation-funded Engineering Research Center tasked with investigating philosophical and social implications of neural engineering research and technologies. Neural devices already in clinical use, such as deep brain stimulators for Parkinson's disease or essential tremor, have spurred healthy debate about such implications. Devices currently under development—such as the BrainGate System of implanted brain sensors coupled to robotics in persons with paralysis, exoskeletons for augmented movement, transcranial do-it-yourself stimulators, closed-loop brain stimulating systems, or even brain-to-brain interfacing—promise to extend and deepen these debates. At our center, brain-computer interfaces are the principal focus of work. Even acknowledging that the clinical translation of neural devices and seamless integration by end users may still largely reside in the future, the potential these devices hold calls for careful early analysis. The launching of the Brain Research through Advancing Innovative Neurotechnologies Initiative in April 2013 provides further impetus for this work. (shrink)

In this essay, our goal is to discover science in Martin Heidegger's Introduction to Metaphysics, lecture notes for his 1935 summer semester course, because, after all, his subject is metaphysica generalis, or ontology, and this could be construed as a theory of the human brain. Here, by means of verbatim quotes from his text, we attempt to show that indeed these lectures can be viewed as suggestion for an objective scientific theory of human perception, the human (...) capacity for deciphering phenomena, ie. hermeneutics in its broadest sense. His added notes from the 1953 edition, all of which are comments, not corrections, imply that he never abandoned these thoughts on metaphysics, despite all of his utterances about a need to overcome it, and their popular interpretations to that effect. In his presentation, he further develops the colorful and intuitive style, an hermeneutic language, that he had created in his earlier work Being and Time. Of human existence he speaks in such expressions as being-there -- ``Dasein" -- and being-in-the-world, the latter term no longer explicit in the 1935 lectures. The lectures can be read as a pre-scientific analysis of how man, being-there, perceives his environment, artfully managing to deal with the manifold challenges posed by the phenomenal structures of the universe. Man attentively recognizes and deciphers their pre-linguistic contents and, while trying to make sense of it all, puts into words his awareness. There are numerous passages in Heidegger's work where he in fairly concrete terms provides us with hints for a perceptive science that, as it turns out and is demonstrated below in this essay, can be explained in terms of recent advances in neuroscience. It would be implausible, even unthinkable, unimaginable, for there not to be found essential agreement between on one hand his philosophical insights gained by hermeneutics of Dasein, into how our brain functions to let us know what's happening & on the other hand, scientific discoveries obtained through anatomy, EEG, fMRI, TMS, electrode implants, etc, of brain structures & functions employed in perception of the momentary scene. A nexus between science and philosophy is provided in Heidegger's definitive treatment of the Logos, here interpreted as a structural version of Platonic forms (Burchard, 2014). This allows for neurolinguistic brain functions to serve as meta-context for Heidegger's being-in-the-world. The logical functions of Dasein's anatomical brain are performed by the logos machine, formerly the human soul, using top-down processing based on a global context, the noumenal cosmos which humans maintain internally. Heidegger's 1942/43 winter semester lectures Parmenides extend in unbroken fashion his 1935 work, proving that he never abandoned, as is widely claimed, his metaphysical avenue of thought. (shrink)

Bidirectional deep brain stimulation (DBS) platforms have enabled a surge in hours of recordings in naturalistic environments, allowing further insight into neurological and psychiatric disease states. However, high amplitude, high frequency stimulation generates artifacts that contaminate neural signals and hinder our ability to interpret the data. This is especially true in psychiatric disorders, for which high amplitude stimulation is commonly applied to deep brain structures where the native neural activity is miniscule in comparison. Here, we characterized artifact sources (...) in recordings from a bidirectional DBS platform, the Medtronic Summit RC + S, with the goal of optimizing recording configurations to improve signal to noise ratio (SNR). Data were collected from three subjects in a clinical trial of DBS for obsessive-compulsive disorder. Stimulation was provided bilaterally to the ventral capsule/ventral striatum (VC/VS) using two independent implantable neurostimulators. We first manipulated DBS amplitude within safe limits (2–5.3 mA) to characterize the impact of stimulation artifacts on neural recordings. We found that high amplitude stimulation produces slew overflow, defined as exceeding the rate of change that the analog to digital converter can accurately measure. Overflow led to expanded spectral distortion of the stimulation artifact, with a six fold increase in the bandwidth of the 150.6 Hz stimulation artifact from 147–153 to 140–180 Hz. By increasing sense blank values during high amplitude stimulation, we reduced overflow by as much as 30% and improved artifact distortion, reducing the bandwidth from 140–180 Hz artifact to 147–153 Hz. We also identified artifacts that shifted in frequency through modulation of telemetry parameters. We found that telemetry ratio changes led to predictable shifts in the center-frequencies of the associated artifacts, allowing us to proactively shift the artifacts outside of our frequency range of interest. Overall, the artifact characterization methods and results described here enable increased data interpretability and unconstrained biomarker exploration using data collected from bidirectional DBS devices. (shrink)

Is the endeavour to restore perceptive brain functions by electronic implants the first step on the way to create bionic cyborgs? Can we augment or multiply our senses by directly contacting computer chips to the brain? Will bio-implants influence and permanently change human psyche?

Objective: Deep brain stimulation targeted to the ventral intermediate nucleus of the thalamus is effective for motor symptoms in essential tremor, but there is limited data on cognitive outcomes. We examined cognitive outcomes in a large cohort of ET DBS patients.Methods: In a retrospective analysis, we used repeated-measures ANOVA testing to examine whether the age of tremor onset, age at DBS surgery, hemisphere side implanted with lead, unilateral vs. bilateral implantations, and presence of surgical complications influenced the cognitive outcomes. (...) Neuropsychological outcomes of interest were verbal memory, executive functioning, working memory, language functioning, visuospatial functioning, and general cognitive function.Results: We identified 50 ET DBS patients; 29 males; the mean age of tremor onset was 35.84 years with a median age of 38 years. The mean age at DBS was 68.18 years. There were 37 unilateral 30 left, seven right, and 13 bilateral brain implantations. In the subgroup analysis, there was a significant interaction between assessment and age of tremor onset ; F = 4.47; p = 0.043 for working memory. The post hoc testing found improvements for younger onset ET. Similarly, there was a significant interaction between assessment and complications vs. no complications subgroups; F = 4.34; p = 0.043 for verbal memory with worsening scores seen for ET patients with complications. The remaining tests were not significant.Conclusion: In this large cohort of ET patients with, DBS was not accompanied by a significant decline in many cognitive domains. These outcomes were possibly related to the selection of patients with normal cognitive functioning before surgery, unilateral DBS implantations for the majority, and selection of patients with optimal response to DBS. (shrink)

Deep Brain Stimulation (DBS) is an effective treatment for advanced Parkinson’s disease. However, identifying stimulation parameters, such as contact and current amplitudes, is time-consuming based on trial and error. Directional leads add more stimulation options and render this process more challenging with a higher workload for neurologists and more discomfort for patients. In this study, a sweet spot-guided algorithm was developed that automatically suggested stimulation parameters. These suggestions were retrospectively compared to clinical monopolar reviews. A cohort of 24 Parkinson’s (...) disease patients underwent bilateral DBS implantation in the subthalamic nucleus at our center. First, the DBS’ leads were reconstructed with the open-source toolbox Lead-DBS. Second, a sweet spot for rigidity reduction was set as the desired stimulation target for programming. This sweet spot and estimations of the volume of tissue activated were used to suggest (i) the best lead level, (ii) the best contact, and (iii) the effect thresholds for full therapeutic effect for each contact. To assess these sweet spot-guided suggestions, the clinical monopolar reviews were considered as ground truth. In addition, the sweet spot-guided suggestions for best lead level and best contact were compared against reconstruction-guided suggestions, which considered the lead location with respect to the subthalamic nucleus. Finally, a graphical user interface was developed as an add-on to Lead-DBS and is publicly available. With the interface, suggestions for all contacts of a lead can be generated in a few seconds. The accuracy for suggesting the best out of four lead levels was 56%. These sweet spot-guided suggestions were not significantly better than reconstruction-guided suggestions (p = 0.3). The accuracy for suggesting the best out of eight contacts was 41%. These sweet spot-guided suggestions were significantly better than reconstruction-guided suggestions (p < 0.001). The sweet spot-guided suggestions of each contact’s effect threshold had a mean error of 1.2 mA. On an individual lead level, the suggestions can vary more with mean errors ranging from 0.3 to 4.8 mA. Further analysis is warranted to improve the sweet spot-guided suggestions and to account for more symptoms and stimulation-induced side effects. (shrink)

Background: Treating medication-refractory freezing of gait in Parkinson’s disease remains challenging despite several trials reporting improvements in motor symptoms using subthalamic nucleus or globus pallidus internus deep brain stimulation. Pedunculopontine nucleus region DBS has been used for medication-refractory FoG, with mixed findings. FoG, as a paroxysmal phenomenon, provides an ideal framework for the possibility of closed-loop DBS.Methods: In this clinical trial, five subjects with medication-refractory FoG underwent bilateral GPi DBS implantation to address levodopa-responsive PD symptoms with open-loop stimulation. (...) Additionally, PPN DBS leads were implanted for CL-DBS to treat FoG. The primary outcome of the study was a 40% improvement in medication-refractory FoG in 60% of subjects at 6 months when “on” PPN CL-DBS. Secondary outcomes included device feasibility to gauge the recruitment potential of this four-lead DBS approach for a potentially larger clinical trial. Safety was judged based on adverse events and explantation rate.Findings: The feasibility of this approach was demonstrated as we recruited five subjects with both “on” and “off” medication freezing. The safety for this population of patients receiving four DBS leads was suboptimal and associated with a high explantation rate of 40%. The primary clinical outcome in three of the five subjects was achieved at 6 months. However, the group analysis of the primary clinical outcome did not reveal any benefit.Interpretation: This study of a human PPN CL-DBS trial in medication-refractory FoG showed feasibility in recruitment, suboptimal safety, and a heterogeneous clinical effect in FoG outcomes. (shrink)

Rationale: Deep brain stimulation (DBS) of the hippocampus is proposed for enhancement of memory impaired by injury or disease. Many pre-clinical DBS paradigms can be addressed in epilepsy patients undergoing intracranial monitoring for seizure localization, since they already have electrodes implanted in brain areas of interest. Even though epilepsy is usually not a memory disorder targeted by DBS, the studies can nevertheless model other memory-impacting disorders, such as Traumatic Brain Injury (TBI). Methods: Human patients undergoing Phase (...) II invasive monitoring for intractable epilepsy were implanted with depth electrodes capable of recording neurophysiological signals. Subjects performed a delayed-match-to-sample (DMS) memory task while hippocampal ensembles from CA1 and CA3 cell layers were recorded to estimate a multi-input, multi-output (MIMO) model of CA3-to-CA1 neural encoding and a memory decoding model (MDM) to decode memory information from CA3 and CA1 neuronal signals. After model estimation, subjects again performed the DMS task while either MIMO-based or MDM-based patterned stimulation was delivered to CA1 electrode sites during the encoding phase of the DMS trials. Each subject was sorted (post hoc) by prior experience of repeated and/or mild-to-moderate brain injury (RMBI), TBI, or no history (control) and scored for percentage successful delayed recognition (DR) recall on stimulated vs. non-stimulated DMS trials. The subject’s medical history was unknown to the experimenters until after individual subject memory retention results were scored. Results: When examined compared to control subjects, both TBI and RMBI subjects showed increased memory retention in response to both MIMO and MDM-based hippocampal stimulation. Furthermore, effects of stimulation were also greater in subjects who were evaluated as having pre-existing mild-to-moderate memory impairment. Conclusion: These results show that hippocampal stimulation for memory facilitation was more beneficial for subjects who had previously suffered a brain injury (other than epilepsy), compared to control (epilepsy) subjects who had not suffered a brain injury. This study demonstrates that the epilepsy/intracranial recording model can be extended to test the ability of DBS to restore memory function in subjects who previously suffered a brain injury other than epilepsy, and support further investigation into the beneficial effect of DBS in TBI patients. (shrink)

This is the second paper in a two-part series describing subject and family perspectives from the CENTURY-S (CENtral Thalamic Deep Brain Stimulation for the Treatment of Traumatic Brain InjURY-Safety) first-in-human invasive neurological device trial to achieve cognitive restoration in moderate to severe traumatic brain injury (msTBI). To participate, subjects were independently assessed to formally establish decision-making capacity to provide voluntary informed consent. Here, we report on post-operative interviews conducted after a successful trial of thalamic stimulation. All (...) five msTBI subjects met a pre-selected primary endpoint of at least a 10% improvement in completion time on Trail-Making-Test Part B, a marker of executive function. We describe narrative responses of subjects and family members, refracted against that success. Interviews following surgery and the stimulation trial revealed the challenge of adaptation to improvements in cognitive function and emotional regulation as well as altered (and restored) relationships and family dynamics. These improvements exposed barriers to social reintegration made relevant by recoveries once thought inconceivable. The study’s success sparked concerns about post-trial access to implanted devices, financing of device maintenance, battery replacement, and on-going care. Most subjects and families identified the need for supportive counseling to adapt to the new trajectory of their lives. (shrink)

Implanting deep brain stimulation (DBS) electrodes in patients with Parkinson’s disease often results in the appearance of a non-infectious, delayed-onset edema that disappears over time. However, the time window between the DBS electrode and DBS stimulating device implant is often used to record local field potentials (LFPs) which are used both to better understand basal ganglia pathophysiology and to improve DBS therapy. In this work, we investigated whether the presence of post-surgery edema correlates with the quality of LFP recordings (...) in eight patients with advanced Parkinson’s disease implanted with subthalamic DBS electrodes. The magnetic resonance scans of the brain after 8.5 ± 1.5 days from the implantation surgery were segmented and the peri-electrode edema volume was calculated for both brain hemispheres. We found a correlation (ρ = −0.81, p < 0.0218, Spearman’s correlation coefficient) between left side local field potentials of the low beta band (11–20 Hz) and the edema volume of the same side. No other significant differences between the hemispheres were found. Despite the limited sample size, our results suggest that the effect on LFPs may be related to the edema localization, thus indicating a mechanism involving brain networks instead of a simple change in the electrode-tissue interface. (shrink)

In sociology, there has been a controversy about whether there is any essential difference between a human being and a tool, or if the tool–user relationship can be defined by co-actor symmetry. This issue becomes more complex when we consider examples of AI and robots, and even more so following progress in the development of various bio-machine hybrid technologies, such as robots that include organic parts, human brain implants, and adaptive prosthetics. It is argued that a concept (...) of autonomous agency based on organismic embodiment helps to clarify the situation. On this view, agency consists of an asymmetrical relationship between an organism and its environment, because the continuous metabolic and regulatory activity of the organism gives rise to its own existence, and hence its specific behavioral domain. Accordingly, most of current technologies are excluded from the class of autonomous agents. Instead, they are better conceptualized as interfaces that mediate our interactions with the world. This has important implications for design: Rather than trying to help humans to achieve their goals by duplicating their agency in artificial systems, it would be better to empower humans directly by enhancing their existing agency and lived experience with technological interfaces that can be incorporated into their embodiment. This incorporation might be especially facilitated by bio-machine hybrid technology that is designed according the principles of biological autonomy and multi-agent coordination dynamics. (shrink)

While new generations of implantable brain computer interface devices are being developed, evidence in the literature about their impact on the patient experience is lagging. In this article, we address this knowledge gap by analysing data from the first-in-human clinical trial to study patients with implanted BCI advisory devices. We explored perceptions of self-change across six patients who volunteered to be implanted with artificially intelligent BCI devices. We used qualitative methodological tools grounded in phenomenology to conduct in-depth, semi-structured (...) interviews. Results show that, on the one hand, BCIs can positively increase a sense of the self and control; on the other hand, they can induce radical distress, feelings of loss of control, and a rupture of patient identity. We conclude by offering suggestions for the proactive creation of preparedness protocols specific to intelligent—predictive and advisory—BCI technologies essential to prevent potential iatrogenic harms. (shrink)

BackgroundThe therapeutic effect of deep brain stimulation (DBS) of the subthalamic nucleus (STN) for Parkinson's disease (PD) is related to the modulation of pathological neural activities, particularly the synchronization in the β band (13–35 Hz). However, whether the local β activity in the STN region can directly predict the stimulation outcome remains unclear.ObjectiveWe tested the hypothesis that low-β (13–20 Hz) and/or high-β (20–35 Hz) band activities recorded from the STN region can predict DBS efficacy.MethodsLocal field potentials (LFPs) were recorded (...) in 26 patients undergoing deep brain stimulation surgery in the subthalamic nucleus area. Recordings were made after the implantation of the DBS electrode prior to its connection to a stimulator. The maximum normalized powers in the theta (4–7 Hz), alpha (7–13 Hz), low-β (13–20 Hz), high-β (20–35 Hz), and low-γ (40–55 Hz) subbands in the postoperatively recorded LFP were correlated with the stimulation-induced improvement in contralateral tremor or bradykinesia–rigidity. The distance between the contact selected for stimulation and the contact with the maximum subband power was correlated with the stimulation efficacy. Following the identification of the potential predictors by the significant correlations, a multiple regression analysis was performed to evaluate their effect on the outcome.ResultsThe maximum high-β power was positively correlated with bradykinesia–rigidity improvement (rs = 0.549, p < 0.0001). The distance to the contact with maximum high-β power was negatively correlated with bradykinesia–rigidity improvement (rs = −0.452, p < 0.001). No significant correlation was observed with low-β power. The maximum high-β power and the distance to the contact with maximum high-β power were both significant predictors for bradykinesia–rigidity improvement in the multiple regression analysis, explaining 37.4% of the variance altogether. Tremor improvement was not significantly correlated with any frequency.ConclusionHigh-β oscillations, but not low-β oscillations, recorded from the STN region with the DBS lead can inform stimulation-induced improvement in contralateral bradykinesia–rigidity in patients with PD. High-β oscillations can help refine electrode targeting and inform contact selection for DBS therapy. (shrink)

Third in a cognitive science series, this peer-reviewed textbook critically surveys historical, current and futuristic attempts to expand the human mind. Areas covered include artificial intelligence, health and medicine, mystical experiences and spirituality, eugenics, brain-computer interfaces, Eastern versus Western psychological approaches and brain studies, virtual reality and implants. The book covers key philosophical, psychological and practical issues.

We estimate that 208,000 deep brain stimulation (DBS) devices have been implanted to address neurological and neuropsychiatric disorders worldwide. DBS Think Tank presenters pooled data and determined that DBS expanded in its scope and has been applied to multiple brain disorders in an effort to modulate neural circuitry. The DBS Think Tank was founded in 2012 providing a space where clinicians, engineers, researchers from industry and academia discuss current and emerging DBS technologies and logistical and ethical issues facing (...) the field. The emphasis is on cutting edge research and collaboration aimed to advance the DBS field. The Eighth Annual DBS Think Tank was held virtually on September 1 and 2, 2020 (Zoom Video Communications) due to restrictions related to the COVID-19 pandemic. The meeting focused on advances in: (1) optogenetics as a tool for comprehending neurobiology of diseases and on optogenetically-inspired DBS, (2) cutting edge of emerging DBS technologies, (3) ethical issues affecting DBS research and access to care, (4) neuromodulatory approaches for depression, (5) advancing novel hardware, software and imaging methodologies, (6) use of neurophysiological signals in adaptive neurostimulation, and (7) use of more advanced technologies to improve DBS clinical outcomes. There were 178 attendees who participated in a DBS Think Tank survey, which revealed the expansion of DBS into several indications such as obesity, post-traumatic stress disorder, addiction and Alzheimer’s disease. This proceedings summarizes the advances discussed at the Eighth Annual DBS Think Tank. (shrink)

In the coming decades humanists and trans-humanists need to wage a global campaign to radicalize the idea of human rights. We need to assert our rights to control our own bodies and brains, whether we choose to change our genders or medicate our brains. We need to assert that the measure of a society’s fairness is how universally available we make the prerequisites for achieving our fullest potential. We need to defend the right to enhance ourselves - whether through (...) education and exercise or genetic engineering and cybernetic implants. We need to extend these “human rights” and citizenship not only to all humans, regardless of nationality, but to all persons, ape, human, posthuman or machine. We need to build the global institutions that can protect the rights of persons, and expand the freedoms they enjoy. (shrink)

This book is a critical examination of the philosophical and moral issues in relation to human enhancement and the various related medical developments that are now rapidly moving from the laboratory into the clinical realm. In the book, the author critically examines technologies such as genetic engineering, neural implants, pharmacologic enhancement, and cryonic suspension from transhumanist and bioconservative positions, focusing primarily on moral issues and what it means to be a human in a setting where technological interventions sometimes (...) impact strongly on our humanity. The author also introduces the notion that death is a process rather than an event, as well as identifies philosophical and clinical limitations in the contemporary determination of brain death as a precursor to organ procurement for transplantation. The discussion on what exactly it means to be dead is later applied to explore philosophical and clinical issues germane to the cryonics movement. Written by a physician/ scientist and heavily referenced to the peer-reviewed medical and scientific literature, the book is aimed at advanced students and academics but should be readable by any intelligent reader willing to carry out some side-reading. No prior knowledge of moral philosophy is assumed, as the various key approaches to moral philosophy are outlined early in the book. (shrink)

Subthalamic nucleus deep brain stimulation is an established therapy for Parkinson’s disease motor symptoms. The ideal site for implantation within STN, however, remains controversial. While many argue that placement of a DBS lead within the sensorimotor territory of the STN yields better motor outcomes, others report similar effects with leads placed in the associative or motor territory of the STN, while still others assert that placing a DBS lead “anywhere within a 6-mm-diameter cylinder centered at the presumed middle (...) of the STN produces similar clinical efficacy.” These discrepancies likely result from methodological differences including targeting preferences, imaging acquisition and the use of brain atlases that do not account for patient-specific anatomic variability. We present a first-in-kind within-patient demonstration of severe mood side effects and minimal motor improvement in a Parkinson’s disease patient following placement of a DBS lead in the limbic/associative territory of the STN who experienced marked improvement in motor benefit and resolution of mood side effects following repositioning the lead within the STN sensorimotor territory. 7 Tesla magnetic resonance imaging data were used to generate a patient-specific anatomical model of the STN with parcellation into distinct functional territories and computational modeling to assess the relative degree of activation of motor, associative and limbic territories. (shrink)