ArticleLiterature Review

Ethical brain stimulation—Neuroethics of deep brain stimulation in research and clinical practice

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  • University of Education, Freiburg
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Abstract

Deep brain stimulation (DBS) is a clinically established procedure for treating severe motor symptoms in patients suffering from end-stage Parkinson's disease, dystonia and essential tremor. Currently, it is tested for further indications including psychiatric disorders like major depression and a variety of other diseases. However, ethical issues of DBS demand continuing discussion. Analysing neuroethical and clinical literature, five major topics concerning the ethics of DBS in clinical practice were identified: thorough examination and weighing of risks and benefits; selecting patients fairly; protecting the health of children in paediatric DBS; special issues concerning patients' autonomy; and the normative impact of quality of life measurements. In exploring DBS for further applications, additionally, issues of research ethics have to be considered. Of special importance in this context are questions such as what additional value is generated by the research, how to realise scientific validity, which patients should be included, and how to achieve an acceptable risk-benefit ratio. Patients' benefit is central for ethical evaluation. This criterion can outweigh very serious side-effects, and can make DBS appropriate even in paediatrics. Because standard test procedures evade central aspects of patients' benefits, measuring quality of life should be supplemented by open in-depth interviews to provide a more adequate picture of patients' post-surgical situation. To examine its entire therapeutic potential, further research in DBS is needed. Studies should be based on solid scientific hypotheses and proceed cautiously to benefit severely suffering patients without putting them to undue risks.

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... As a consequence neuro-interventions trigger and raise ethical questions that are not also triggered by other biomedical technologies. In particular ethical questions have been raised that target the way in which DBS, and potentially other neuromodulation techniques, could influence people's identities, their sense of agency and who they are as a person (e.g., Baylis, 2015;Bell, Mathieu, & Racine, 2009;Clausen, 2010;Galert, 2015;Glannon, 2009;Nuffield Council on Bioethics, 2013;Schechtman, 2010;Schermer, 2011;Synofzik, 2015b;Witt, Kuhn, Timmermann, Zurowski, & Woopen, 2013). Therefore, conditions that can be linked to brain functioning pose a particular challenge. ...
... This chapter will elaborate on what it means to meet traditional medical ethical requirements in the context of DBS. That is, it will be discussed what it means to 'respect autonomy', to safeguard beneficence and non-maleficence and how to live up to the requirements of justice (Beauchamp & Childress, 2009;Bell et al., 2009;Clausen, 2010;Synofzik & Schlaepfer, 2008). In this sense, the merits of DBS are discussed in light of its risks and side-effects and compared to possible alternatives, such as pharmacological treatment, other forms of neuromodulation and psychotherapy. ...
... Individuals have rights of bodily and mental integrity, which entails that others may not intervene in their bodies or the functioning of their minds without their informed and well-considered consent (Bell et al., 2009;Clausen, 2010). For competent patients this right for self-determinations means that doctors may start treatments only after they have informed them about their health conditions, reasonable prospects and any treatment options, pointing out possible benefits and expected effects, as well as potential risks and side-effects. ...
Chapter
Since its first applications in humans, DBS has triggered a plethora of ethical questions and concerns and stimulated extensive ethical debates as to its significance and desirability. The main ethical goal is to guide and support responsible decision-making in clinical DBS treatment, as well as related medical research, and to raise awareness about salient ethical issues. Traditional medical ethics consists of the three basic principles of respect for autonomy, beneficence/nonmaleficence and justice. In the context of DBS, these principles require specific attention as to what exactly it means to “respect autonomy,” to safeguard beneficence and nonmaleficence, and to live up to the requirements of justice. Taking the risks and side effects of DBS into account and comparing this treatment to possible alternative treatments is crucial. Given the increasing interest in applying DBS to psychiatric disorders, research ethical questions have been put on the agenda. The status of the brain also gave rise to the expression of profound ethical concerns, particularly regarding potential changes in patients’ personal identity. However, different understandings of this very concept lead to diverging evaluations of the ethical value of potentially identity-modifying techniques. Independent ethical substudies or integral add-on projects in DBS research can advance systematic ethical thought regarding ongoing research endeavors and upcoming new applications.
... 3 Like any neurosurgical procedure, DBS is associated with perioperative risks, as well as risks associated with the long-term implantation of the device. 4 Stimulation has also been associated with adverse cognitive, behavioural, psychiatric and psychosocial effects. 4 In particular, the ethical discussion concerning DBS has focused on its association with adverse psychosocial effects on the patient's self-conception. ...
... 4 Stimulation has also been associated with adverse cognitive, behavioural, psychiatric and psychosocial effects. 4 In particular, the ethical discussion concerning DBS has focused on its association with adverse psychosocial effects on the patient's self-conception. 5 There is emerging data of such effects arising in psychiatric applications of DBS; 6 these effects may also be complicated in this context by the fact that the targeted conditions can be egosyntonic. ...
... This means that it is crucial that the assessments of capacity to consent to DBS are sensitive to the value changes that patients may undergo over the course of long-term treatment. Second, while adverse psychosocial effects on the patient's self-conception following DBS have been reported, 4 there is less evidence associating NMD with such effects. 31 Although there is presently little comparative evidence to allow us to make accurate likewise comparisons in this regard, if further evidence established that DBS does have stronger adverse effects on personality or self-conception than NMD, this would lend further support to the thought that considerations about how the patient is weighing the values at stake in their treatment decisions are particularly salient in DBS. ...
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Under the current Mental Health Act of England and Wales, it is lawful to perform deep brain stimulation in the absence of consent and independent approval. We argue against the Care Quality Commission's preferred strategy of addressing this problematic issue, and offer recommendations for deep brain stimulation-specific provisions in a revised Mental Health Act. Declaration of interest T.A. is a paid consultant for Boston Scientific, Medtronic and St. Jude Medical. He has received honoraria from Abbott, Boston and Medtronics and served as consultant to all three.
... DBS in TS seems to have a promising future in terms of tic reduction, however, it raises several ethical questions that need continuing discussion especially in 3) protecting the health of children in paediatric DBS, 4) special issues concerning patient's autonomy, and 5) the normative impact of quality of life measurements [53]. When discussing the first topic: selecting patients fairly, one of the first questions is whether DBS should be indicated for adolescent patients with TS, given the chances of natural remission during adolescence. ...
... Thorough selection of patients who should be offered DBS is an essential requirement for a successful intervention from a clinical as well as an ethical perspective. In general, patient selection should optimize the individual risk-benefit ratio [53]. ...
... The patient's benefit is central in the ethical evaluation. This criterion can outweigh risks and side-effects, and can make DBS appropriate even in adolescent TS patients with a chance of natural remission [53]. ...
Article
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Introduction: Tourette Syndrome (TS) is a childhood onset disorder characterized by vocal and motor tics and often remits spontaneously during adolescence. For treatment refractory patients, Deep Brain Stimulation (DBS) may be considered. Methods and results: We discuss ethical problems encountered in two adolescent TS patients treated with DBS and systematically review the literature on the topic. Following surgery one patient experienced side effects without sufficient therapeutic effects and the stimulator was turned off. After a second series of behavioural treatment, he experienced a tic reduction of more than 50%. The second patient went through a period of behavioural disturbances that interfered with optimal programming, but eventually experienced a 70% tic reduction. Sixteen DBS surgeries in adolescent TS patients have been reported, none of which pays attention to ethical aspects. Discussion: Specific ethical issues arise in adolescent TS patients undergoing DBS relating both to clinical practice as well as to research. Attention should be paid to selecting patients fairly, thorough examination and weighing of risks and benefits, protecting the health of children and adolescents receiving DBS, special issues concerning patient's autonomy, and the normative impact of quality of life. In research, registration of all TS cases in a central database covering a range of standardized information will facilitate further development of DBS for this indication. Conclusion: Clinical practice should be accompanied by ongoing ethical reflection, preferably covering not only theoretical thought but providing also insights in the views and perspectives of those concerned, that is patients, family members and professionals.
... Most of the time, unlike what occurs in clinical drug trials (especially in phase I), the only candidates for an implant trial are the patients themselves. Often, they have already experienced decades of suffering and treatment (Clausen 2010). ...
... Just as with other active implantable devices, DBS development required an experiential learning process, as attested by the importance of "case reports" in the literature on the subject (Bell et al. 2009). Hence, incidental discoveries gave rise to the idea that DBS might be used to treat problems like OCD, addiction, or memory disorders (Bell et al. 2009;Clausen 2010;Hariz 2012;Moutaud 2009Moutaud , 2014Foley 2015). For this treatment, case reports played such a decisive role that a claim has been made to demand more systematic and centralized publication of findings, including findings on individual patients or on very small cohorts (Schlaepfer and Fins 2010). ...
... Yet where DBS is concerned, an overview of the literature dedicated to applied ethics for the protection of people undergoing neurostimulation does not lead to such a conclusion. The same conceptual resources are present: the principles of non-malfeasance, of beneficence, of personal autonomy, and of benefit-vs-risk analysis (Bell et al. 2009(Bell et al. , 2011Clausen 2010;Kim 2013;Synofzik and Schlaepfer 2011;Cabrera et al. 2014;Synofzik 2013Synofzik , 2015Unterrainer and Oduncu 2015;Foley 2015). The authors admit that the persons to whom these principles are applied are themselves in a situation to be simultaneously patients and participants in research. ...
Article
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In the past 50 years, an ethical-legal boundary has been drawn between treatment and research. It is based on the reasoning that the two activities pursue different purposes. Treatment is aimed at achieving optimal therapeutic benefits for the individual patient, whereas the goal of scientific research is to increase knowledge, in the public interest. From this viewpoint, the patient's experience should be clearly distinguished from that of a participant in a clinical trial. On this premise, two parallel and mutually exclusive regimes have been established. Yet in the case of deep brain stimulation (DBS), this presentation is a poor fit, for both the patient's lived experience and medical practice and research. The frictions may be explained by the specificities of the treatment (including surgery and medical devices) and of the pathologies concerned (chronic and evolutive), and by the characteristics of the medical team implementing the treatment. These particularities challenge the dominant frame of reference in medical bioethics and cause difficulties for the current legal framework in fulfilling its dual role: to protect patients while supporting the development of innovative treatments. The dominant model is still the clinical trial for medication safety and legal requirements of drug market regulation. However, DBS forces us to reflect on a medical device that is permanently implanted in the brain by highly specialized multi-disciplinary neurosurgical teams, for the treatment of chronic evolutive diseases. These devices demand fine-tuning on a case-by-case basis and there is still a lot to discover about why DBS is effective (or not). As a result, the wall between treatment and research is osmotic: many discoveries are made incidentally, in the course of treatment. The following study begins with these observations, and suggests that we review legal provisions (especially in French and United States law) so that they are better adapted to the first-person needs and experience of the patient undergoing brain stimulation.
... Obsessive-Compulsive Disorder, Major Depression, addictions) (Williams & Okun, 2013) symptoms. Yet, despite the remarkable efficacy in general, psychological (mal)adaptations to the treatment might occur (Clausen, 2010;Klaming & Haselager, 2013;Mackenzie, 2011;Schermer, 2011;Witt et al., 2008;Witt, Kuhn, Timmermann, Zurowski, & Woopen, 2013b), in addition to operative and post-operative surgical complications (Doshi, 2011). As the literature extensively reports, the vast majority of the side effects can be usually addressed during the post-operative follow-up by optimizing the stimulator's parameters (Clausen, 2010;Goodman & Alterman, 2012). ...
... Yet, despite the remarkable efficacy in general, psychological (mal)adaptations to the treatment might occur (Clausen, 2010;Klaming & Haselager, 2013;Mackenzie, 2011;Schermer, 2011;Witt et al., 2008;Witt, Kuhn, Timmermann, Zurowski, & Woopen, 2013b), in addition to operative and post-operative surgical complications (Doshi, 2011). As the literature extensively reports, the vast majority of the side effects can be usually addressed during the post-operative follow-up by optimizing the stimulator's parameters (Clausen, 2010;Goodman & Alterman, 2012). Nevertheless, in some cases the psychological well-being of the treated subjects cannot be optimally preserved, and setting the stimulation parameters might be poorly effective. ...
... According to some authors (e.g. (Clausen, 2010)), psycho-social effects have the largest impact (quantitatively speaking) among the reported side effects. These effects could be caused by the stimulation itself, but perhaps also, or even instead, be a consequence of a psychological reaction, where the patients might experience discomfort in relation to the knowledge of having an implanted stimulator. ...
... The US Food and Drug Administration (FDA) approved the use of the deep brain stimulator for refractory Parkinson's disease in 2002 4 , while clinical investigators are conducting more and more trials for its further use in obsessive compulsive disorders (OCD), depression, and traumatic brain injury [4][5][6] . However, the "boundary between experimental work and therapeutic deployment" lies not only on approval of the regulatory authorities like FDA 3 , but also on the consensus of the medical community that the putative treatment is effective and safe 2,3,4 , and that the intended benefits will appear without any short or long-term adverse effects 2,3,7,8 . In recent years, neurosurgical ethics has become more relevance as changes in society and technology have brought some inevitable questions into focus 4 . ...
... Deep brain stimulation (DBS), a form of neuromodulation, is a functional neurosurgical approach in which a high-frequency electrical current stimulates targeted brain structures for therapeutic benefit 7,8,14 . The system include an implanted brain electrode (into deep brain regions) by using stereotactic techniques and a pacemaker-like implanted pulse generator (IPG), which is typically placed subdermally below the clavicle 7,10,14 . ...
... Although physiological mechanism of DBS is not fully understood, it is generally assumed that it works through excitation and/or inhibition of neuronal cell bodies adjacent to the electrode and on nearby axons, too 10,12,14,15 . This intervention is based on the empirical observation that specific brain targets stimulated by electro-magnetic wave tends to mimic the effect of a lesion without the need for destroying brain tissue 8,14,15 . Low-frequency stimulation appears to be effective, while high-frequency stimulation may reduce activity and induce functional lesion; however, such simplistic view is controversial to date 10,13,15 . ...
Article
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Deep brain stimulation (DBS), a form of neuromodulation, is recognized as a therapeutic venture for the management of chronic pain, the evaluation and management of epilepsy, and the treatment of Parkinson’s disease and other movement disorders. Clinical investigators are conducting more trials for its further use in obsessive compulsive disorders (OCD), depression, and traumatic brain injury. It is imperative to address the ethical concerns of such innovative neurosurgical treatment and research with human experimentation in the respective arena. The term ‘neurosurgical ethics’ is a moral approach towards ethical problems emerging from our day to day neurosurgical practice and research as well as current and future innovation in the field. The review paper outlined the procedures of DBS, as currently used in therapeutic and experimental applications and to discuss the ethical concerns regarding this innovative procedure.
... In the last 15 years, there have been a number of studies investigating brain function by systematically exploring the dynamical responses to controlled artificial external perturbations of different brain regions and combining them with whole-brain neuroimaging [13][14][15][16][17][18] . There is a wide range of perturbation possibilities available, from easier to perform perturbation methods such as sensory stimulation and task instructions, to more invasive and costly methods, such as transcranial magnetic stimulation (TMS) in healthy human subjects to deep brain stimulation (DBS) in patients [19][20][21][22] . Also pharmacological studies inducing an anaesthetic state, which can also be considered as a perturbation to the brain, exist in human 23 as well as in the non-human primate 24 exploring the dynamic repertoires of the brain. ...
... The advantage of direct controlled artificial perturbations of specific brain regions is the systematic exploration of the provoked dynamical responses. These direct approaches have, however, been limited to transcranial magnetic stimulation (TMS) in healthy human subjects and to deep brain stimulation (DBS) in patients [19][20][21][22] . ...
Article
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Lysergic acid diethylamide (LSD) is a potent psychedelic drug, which has seen a revival in clinical and pharmacological research within recent years. Human neuroimaging studies have shown fundamental changes in brain-wide functional connectivity and an expansion of dynamical brain states, thus raising the question about a mechanistic explanation of the dynamics underlying these alterations. Here, we applied a novel perturbational approach based on a whole-brain computational model, which opens up the possibility to externally perturb different brain regions in silico and investigate differences in dynamical stability of different brain states, i.e. the dynamical response of a certain brain region to an external perturbation. After adjusting the whole-brain model parameters to reflect the dynamics of functional magnetic resonance imaging (fMRI) BOLD signals recorded under the influence of LSD or placebo, perturbations of different brain areas were simulated by either promoting or disrupting synchronization in the regarding brain region. After perturbation offset, we quantified the recovery characteristics of the brain area to its basal dynamical state with the Perturbational Integration Latency Index (PILI) and used this measure to distinguish between the two brain states. We found significant changes in dynamical complexity with consistently higher PILI values after LSD intake on a global level, which indicates a shift of the brain's global working point further away from a stable equilibrium as compared to normal conditions. On a local level, we found that the largest differences were measured within the limbic network, the visual network and the default mode network. Additionally, we found a higher variability of PILI values across different brain regions after LSD intake, indicating higher response diversity under LSD after an external perturbation. Our results provide important new insights into the brain-wide dynamical changes underlying the psychedelic state - here provoked by LSD intake - and underline possible future clinical applications of psychedelic drugs in particular psychiatric disorders.
... These involve not only the surgical operative and post-operative aspects (Doshi, 2011), but also the chance of some behavioral/psychological alterations (Clausen, 2011;Klaming & Haselager, 2013;Mackenzie, 2011;Schermer, 2011;Witt et al., 2008). Although the majority of side effects can be, and effectively are, addressed in the postoperative follow-up by fine tuning the stimulatory parameters (Clausen, 2010;Goodman & Alterman, 2012), some others seem to be harder to remove by tweaking the stimulation. These cases, besides having been extensively discussed within the clinical/scientific literature, have drawn the attention of a number of neuroethicists [e.g. ...
... These cases, besides having been extensively discussed within the clinical/scientific literature, have drawn the attention of a number of neuroethicists [e.g. (Baylis, 2013;Clausen, 2010;Klaming & Haselager, 2013;Mecacci & Haselager, 2014;Schermer, 2009a)]. It is both conceptually and empirically 1 problematic to determine to what extent this maladaptation can be attributed to a psychological reaction to the new situation or to the effect of the electrical stimulation on neural mechanisms. ...
Chapter
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Deep Brain Stimulation is one of the latest promising and widely discussed therapeutic neurotechnologies. Yet, along with its remarkable efficacy comes a number of complications. Besides surgical operative and post–operative difficulties, behavioral/psychological alterations can occur. In a recent paper we suggested the idea that patients’ endorsement of certain conceptual frameworks might conceivably affect the degree of psychological adaptation to the implanted stimulator. In particular, we argued that the way mind/body relationship is framed in patients’ psychology could play a role in modulating the degree of adaptation to the therapy. In this chapter, we will summarize our position, address several responses our paper received and clarify our position further.
... BCIs that are used for the treatment of neurological disorders have been shown to produce some changes in self-identification of some patients. For example, some patients that used BCIs for treatment of Parkinson's disease have expressed reservations about identifying with their condition before the use of BCIs (Clausen, 2010(Clausen, : 1155. There are also known minor cases of side effects of the usage of older versions of BCIs. ...
... Some researchers reported different and progressive changes of the personal characteristic of some patients that were using neurostimulation devices. The symptoms included loss of social control, hypersexuality, compulsive disorders, cognition alterations and aggression (Clausen, 2010(Clausen, : 1159. Such cases can be seen as prime examples of procedures, or technologies that can directly endanger personal identity. ...
... Beyond the insights obtained under natural conditions, direct artificial perturbations allow for the systematic exploration of dynamical responses elicited by controlled perturbative protocols. However, such perturbative approaches are generally limited to TMS in healthy humans (Siebner et al., 2009), or DBS in human patients, due to ethical considerations (Kringelbach et al., 2007b;Clausen, 2010;Fox et al., 2014). Combining these direct stimulation techniques with whole-brain neuroimaging allows exploring how the system leaves the resting equilibrium by characterizing the resulting dynamics in terms of complexity and latencies using TMS-EEG (Ilmoniemi et al., 1997;Massimini et al., 2005;Litvak et al., 2007;Casali et al., 2013), DBS-MEG (Kringelbach et al., 2007a;Mohseni et al., 2012) and DBS-fMRI (Saenger et al., 2017b). ...
... The model is previously adjusted to the basal activity recorded with fMRI in each brain state, here wakefulness and deep sleep, resulting in two distinct models representative of each unperturbed brain state (Jobst et al., 2017). These models can then be exhaustively perturbed in silico without the ethical and safety constrains of in vivo perturbations (Clausen, 2010;. Previous studies have used whole-brain computational models to simulate the effects of structural lesions, i.e. by removing links or nodes, and studying its impact in whole-brain dynamics (Cabral et al., 2012a;Vasa et al., 2015;Aerts et al., 2016;Deco et al., 2017c). ...
Article
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Human neuroimaging research has revealed that wakefulness and sleep involve very different activity patterns. Yet, it is not clear why brain states differ in their dynamical complexity, e.g. in the level of integration and segregation across brain networks over time. Here, we investigate the mechanisms underlying the dynamical stability of brain states using a novel off-line in silico perturbation protocol. We first adjust a whole-brain computational model to the basal dynamics of wakefulness and deep sleep recorded with fMRI in two independent human fMRI datasets. Then, the models of sleep and awake brain states are perturbed using two distinct multifocal protocols either promoting or disrupting synchronization in randomly selected brain areas. Once perturbation is halted, we use a novel measure, the Perturbative Integration Latency Index (PILI), to evaluate the recovery back to baseline. We find a clear distinction between models, consistently showing larger PILI in wakefulness than in deep sleep, corroborating previous experimental findings. In the models, larger recoveries are associated to a critical slowing down induced by a shift in the model's operation point, indicating that the awake brain operates further from a stable equilibrium than deep sleep. This novel approach opens up for a new level of artificial perturbative studies unconstrained by ethical limitations allowing for a deeper investigation of the dynamical properties of different brain states.
... However, like any medical treatment, DBS is not without side-effects and risks. In addition to the perioperative risks of the procedure itself, DBS has in some cases been observed to have various adverse cognitive, psychiatric, behavioural or psycho-social side-effects (Clausen 2010). Many of these side-effects and risks have received considerable ethical attention elsewhere (Baylis 2013;Clausen 2010;Gilbert 2013Gilbert , 2017Gilbert et al. 2017;Klaming and Haselager 2010;Kraemer 2013a;Lipsman and Glannon 2013;Schermer 2011), in light of the issues they raise for personal identity, responsibility, autonomy and well-being. ...
... In addition to the perioperative risks of the procedure itself, DBS has in some cases been observed to have various adverse cognitive, psychiatric, behavioural or psycho-social side-effects (Clausen 2010). Many of these side-effects and risks have received considerable ethical attention elsewhere (Baylis 2013;Clausen 2010;Gilbert 2013Gilbert , 2017Gilbert et al. 2017;Klaming and Haselager 2010;Kraemer 2013a;Lipsman and Glannon 2013;Schermer 2011), in light of the issues they raise for personal identity, responsibility, autonomy and well-being. ...
Article
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'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.
... 41 Although attempts at stimulation of the brain occurred earlier, 7,21 the marking of a new starting point for deep brain stimulation (DBS) came with a report published in 1987, 6 and since then DBS has revolutionized the treatment of movement disorders, in particular Parkinson's disease and essential tremor (ET). 11 In DBS, different brain structures are targeted depending on the symptoms of the patient. The ventral intermediate nucleus (VIM) of the thalamus is the established target for ET treatment. ...
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Objective: The ventral intermediate nucleus (VIM) of the thalamus is currently the established target in the use of deep brain stimulation (DBS) to treat essential tremor (ET). In recent years, the caudal zona incerta (cZi), a brain target commonly used during the lesional era, has been revived as the primary target in a number of DBS studies that show evidence of the efficacy of cZi targeting in DBS treatment for controlling the symptoms of ET. The authors sought to obtain comprehensive neuropsychological data and thoroughly investigate the cognitive effects of cZi targeting in patients with ET treated with DBS. Methods: Twenty-six consecutive patients with ET who received DBS with cZi as the target at our department from December 2012 to February 2017 were included in this study. All patients were assessed using a comprehensive neuropsychological test battery covering the major cognitive domains both preoperatively and 12 months postoperatively. Results: The results show no major adverse effects on patient performance on the tests of cognitive function other than a slight decline of semantic verbal fluency. Conclusions: This study indicates that the cZi is a safe target from a cognitive perspective in the treatment of ET with DBS.
... There are two type of VNS -invasive and non-invasive. Even the invasive type is a cheaper, easier and less risky procedure compared to DBS surgery because the electrode implantation for VNS is not intracranial, but peripheral where cervical section of the vagus nerve is surgically accessed in the carotid area of the neck (Clausen, 2010;Giordano et al., 2017). The non-invasive type of VNS involves transcutaneous vagus nerve stimulation (Hein et al., 2013;Kraus et al., 2013;Rong et al., 2016). ...
Article
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The basal forebrain is one of the three major brain circuits involved in episodic memory formation together with the hippocampus and the diencephalon. The dysfunction of each of these regions is known to cause anterograde amnesia. While the hippocampal pyramidal neurons are known to encode episodic information and the diencephalic structures are known to provide idiothetic information, the contribution of the basal forebrain to memory formation has been exclusively associated with septo-hippocampal cholinergic signaling. Research data from the last decade broadened our understanding about the role of septal region in memory formation. Animal studies revealed that septal neurons process locomotor, rewarding and attentional stimuli. The integration of these signals results in a systems model for the mnemonic function of the medial septum that could guide new therapeutic strategies for basal forebrain impairment (BFI). BFI includes the disorders characterized with basal forebrain amnesia and neurodegenerative disorders that affect the basal forebrain. Here, we demonstrate how the updated model of septal mnemonic function can lead to innovative translational treatment approaches that include pharmacological, instrumental and behavioral techniques.
... 5 6 DBS poses a number of perioperative and postoperative risks 7 that have been widely discussed elsewhere in the ethics literature. [8][9][10] Yet, for many patients, the potential benefits of DBS may plausibly outweigh these risks. ...
Article
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Deep brain stimulation (DBS) is frequently described as a ‘reversible’ medical treatment, and the reversibility of DBS is often cited as an important reason for preferring it to brain lesioning procedures as a last resort treatment modality for patients suffering from treatment-refractory conditions. Despite its widespread acceptance, the claim that DBS is reversible has recently come under attack. Critics have pointed out that data are beginning to suggest that there can be non-stimulation-dependent effects of DBS. Furthermore, we lack long-term data about other potential irreversible effects of neuromodulation. This has considerable normative implications for comparisons of DBS and brain lesioning procedures. Indeed, Devan Stahl and colleagues have recently argued that psychiatric DBS should be subject to the same legal safeguards as other forms of psychosurgery, supporting their position by forcibly criticising the claim that DBS is reversible. In this paper, I respond to these criticisms by first clarifying the descriptive and evaluative elements of the reversibility claim that supporters of DBS might invoke, and the different senses of ‘reversibility’ that we might employ in discussing the effects of medical procedures. I go on to suggest that it is possible to defend a nuanced version of the reversibility claim. To do so, I explain how DBS has some effects that are stimulation dependent in the short term, and argue that these effects can have significant normative implications for patient well-being and autonomy. I conclude that we should not abandon a nuanced version of the reversibility claim in the DBS debate.
... One of the challenges facing the development of a functional and user-friendly device is to ensure that the device only vocalizes speech that the person intends to express [4]. Another challenge relates to the phenomenology of intentional action and what it means for a person to be in control of their actions [5][6][7][8]. If a person depends upon deep-brain stimulation (DBS) to control the symptoms of Parkinson's disease, to speak, or to move, the person might feel as though they are "out-of-the-loop" and alienated from their own bodily movement. ...
Article
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A brain-computer interface (BCI) designed to restore motor function detects neural activity related to intended movement and thereby enables a person to control an external device, for example, a robotic limb, or even their own body. It would seem legitimate, therefore, to describe a BCI as a system that translates thought into action. This paper argues that present BCI-mediated behavior fails to meet the conditions of intentional physical action as proposed by causal and non-causal theories of action. First, according to the causal theory of action physical actions are bodily movements that are causally related to a person’s intentions. It can be argued, however, that the proximate cause of action in present BCI-mediated behavior is not the person’s intention, and that the behavior fails to meet the conditions of reliability, sensitivity and difference-making. Second, BCI-mediated behavior can be accommodated by a Volitionist account of action if we can equate imagining movement with trying to move. The argument presented is that the novelty, and limited functionality and sensory feedback of present BCIs challenges this equation.
... Due to the dearth of long-term evidence of chronic brain stimulation in children, there is expected caution exercised prior to the use of DBS for epilepsy [27]. The youngest patient reported to undergo DBS for epilepsy was 4 years old [10], although it is unknown if there is a minimum age. ...
Article
Neuromodulatory strategies are increasingly adopted for the treatment of intractable epilepsy in children. These encompass a wide range of treatments aimed at externally stimulating neural circuitry in order to decrease seizure frequency. In the current review, the authors discuss the evidence for invasive neuromodulation, namely vagus nerve and deep brain stimulation in affected children. Putative mechanisms of action and biomarkers of treatment success are explored and evidence of the efficacy of invasive neuromodulation is highlighted.
... Differences in silico protocols can be assessed to study how different brain states react to external perturbations such as shifting the local dynamics in the opposite direction, node by node perturbation 78,79 , nonsustained perturbations 47,80 or perturbing with external strength dependent periodic force 47,77 . Notably, the perturbative approach allows for the exploration of brain responses elicited by in silico protocols which are not limited by ethical constraints of in vivo stimulations 81,82 . Furthermore, the differential sensitivity of each brain state of external perturbations could potentially serve as a specific biomarker that reveals features of their dynamical complexity. ...
Article
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Significant advances have been made by identifying the levels of synchrony of the underlying dynamics of a given brain state. This research has demonstrated that non-conscious dynamics tend to be more synchronous than in conscious states, which are more asynchronous. Here we go beyond this dichotomy to demonstrate that different brain states are underpinned by dissociable spatiotemporal dynamics. We investigated human neuroimaging data from different brain states (resting state, meditation, deep sleep and disorders of consciousness after coma). The model-free approach was based on Kuramoto’s turbulence framework using coupled oscillators. This was extended by a measure of the information cascade across spatial scales. Complementarily, the model-based approach used exhaustive in silico perturbations of whole-brain models fitted to these measures. This allowed studying of the information encoding capabilities in given brain states. Overall, this framework demonstrates that elements from turbulence theory provide excellent tools for describing and differentiating between brain states.
... In interviews conducted with participants with PD before and up to 24 months after DBS, participants reported dissatisfaction despite objective improvements in symptoms Schupbach et al., 2006). This apparent contradiction has been attributed to the impact of unrealistic expectations, where the hopes of a cure or improvements beyond those anticipated by the clinical team affect satisfaction with the outcome (Clausen, 2010;Montel & Bungener, 2009). Difficulties adjusting and re-integrating into daily life could also impact on level of satisfaction with the treatment Schupbach et al., 2006), demonstrating the individualised nature of PD and DBS experiences. ...
Article
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Background: Deep brain stimulation is a surgical treatment for Parkinson's disease. Its impacts on motor symptoms are widely reported; however, little is known about the broader impact of deep brain stimulation on the community lives of people with Parkinson's disease. Lifespace is a measure of lived community mobility, providing an indication of community access and participation. Aims: This pilot study explored the feasibility of remotely monitoring the qualitative and quantitative community outcomes related to deep brain stimulation. Methods: A longitudinal mixed methods study with a convergent design was undertaken exploring the lifespace, quality of life, life satisfaction and lived experiences of people with Parkinson's disease before and after deep brain stimulation. Data were collected through questionnaires, semi-structured interviews and a smartphone-based application which collected geolocation data. Results: Quantitative and qualitative data from eight participants living with Parkinson's disease were analysed and integrated. At baseline, participants had a median age of 68 years and a median Hoehn and Yahr score of 2. Measuring a range of community-based outcomes indicated different change trajectories for individuals across outcomes. Key content areas were developed from the qualitative data: participation in occupations and travel and home. This study indicates the potential value of including geolocation data-based lifespace collection in metropolitan and regional areas. Conclusions: Monitoring lifespace in conjunction with subjective measures provides insights into the complex and individually varied experiences. Further research could explore the impacts of deep brain stimulation on occupations and community participation to gain a deeper understanding of the related needs and support clinical approaches.
... The identification of these factors as particularly relevant to perceptions of DBS indicates that these variables should be monitored in potential clinical trials of DBS for adolescents-particularly variables that have the potential to be overlooked or that may be difficult to capture, such as personality changes or impact on development. Such factors are consistent with primary ethical issues around DBS that have been identified in the previous literature, such as concerns about side effects and weighing risks and benefits, especially in children where long-term effects and complications are unknown (Clausen 2010) (Table 5). ...
Article
Objective: The present study aims to understand perceptions of deep brain stimulation (DBS) for severe obsessive-compulsive disorder (OCD) in adolescents among two groups: parents of children with a history of OCD and adults with a history of OCD. Methods: Two hundred sixty participants completed a questionnaire exploring their treatment history, relevant symptom severity, DBS knowledge, and DBS attitudes using an acceptability scale and a series of statements indicating levels of willingness or reluctance to consider DBS for adolescents with severe OCD or severe epilepsy. Results: Overall, participants found DBS to be fairly acceptable for adolescents with severe OCD, with 63% reporting at least 7/10 on a 0-10 acceptability Likert scale. Respondents were more willing to consider DBS for epilepsy than for OCD. Several factors were associated with greater willingness to consider DBS for OCD, including familiarity with DBS, the presence of suicidal thoughts, assurances of daily functioning improvements, and assurances of substantial symptom reduction. Concerns about safety, personality changes, and long-term effects on the body were associated with greatest reluctance to consider DBS for OCD. Conclusions: Our findings support the importance of increasing parents' familiarity with DBS, monitoring factors participants identified as most important to their DBS perceptions in future DBS research, and communicating benefits and risks clearly. We also highlight the need for further research on perceptions of DBS for severe and refractory OCD in adolescents.
... This group would include those who definitively think it will not be possible (De Melo-Martin & Salles, 2015) and those who think it will most likely not be possible (Crockett, 2014;Sparrow, 2014). One of the reasons given by members of this second group is that it would be impossible -or inadvisable, even if possible -due to the complexity of human moral psychology (Zarpentine, 2013;Young & Duncan, 2012;Lechner, 2014;Bronstein, 2010;Andreadis, 2010;Arnhart, 2010;Sprinkle, 2010) Those who hold this view tend to argue that the side effects, risks or negative consequences will be too great (Harris, 2011;Clausen, 2010;Barilan, 2015;Jones), or, that moral bioenhancement will morally worsen us (Agar, 2015a;Chan & Harris, 2011, Hubbeling, 2009. 16 There are a number of criticisms of such virtue ethics approaches and addressing this matter is beyond the scope of my dissertation; however, it is interesting to note that this approach has been criticised by Harris (2013c). ...
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It has been argued, in the bioethics literature, that traditional forms of moral instruction and development are no longer adequate in equipping humanity to address the urgent nature of the ethical problems facing contemporary societies. Rather than continuing to rely upon these supposedly ineffective methods, we should explore the possibility of biologically enhancing our morality. This would entail both decreasing the likelihood that we would wish to cause harm to others as well as increasing our motivation to do good. The proponents of moral bioenhancement argue that the best way of achieving this would be to isolate which affective dispositions, that are associated with moral traits, are susceptible to biological modification and to biologically enhance these dispositions. However, despite the presence of strong consequentialist arguments in favour of moral bioenhancement, it has elicited a variety of ethical concerns as well as conceptual and practical problems that would have to be addressed for it to become a coherent possibility. An ethical concern that has been raised in the literature is the concern that moral bioenhancement is wrong, in principle, and regardless of any benefits it could produce, because it risks negatively impacting phenomena that are regarded as intrinsically valuable. In particular, the concern is that moral bioenhancement could impact our moral autonomy, and thus, threaten human morality as such. This concern is based upon the view that the conditions for the exercise of autonomous moral behaviour, and thus morality itself, lie in the deliberation and choice that must be freely made in the face of competing demands. In other words, if it became possible to biologically increase our motivation to do good, thereby increasing the likelihood that we act in a way that is regarded as morally desirable, could our resultant behaviour still be regarded as morally autonomous; or, is morality solely a product of our given, unaltered biological predispositions, working in conjunction with traditional mechanisms of moral education? Will morality as we know it disappear if moral bioenhancement becomes a possibility? This dissertation contributes towards the literature through a comprehensive review in which particular conceptual, philosophical and empirical problems are addressed, as well as by providing a structured discussion of the practical and theoretical ethical concerns regarding moral bioenhancement. The dissertation includes a substantive definition of moral bioenhancement and makes further independent contributions through the analysis and application of a coherence theory of autonomy to ascertain the status for moral autonomy of various outcomes of moral bioenhancement interventions. From this analysis, a checklist of interventions that could be potentially inimical to autonomy, in terms of their outcomes, is constructed. The conclusion is that in certain cases, moral bioenhancement could produce an increase, rather than a decrease, in the level of autonomy experienced by individuals.
... Differences in silico protocols can be assessed to study how different brain states react to external perturbations such as shifting the local dynamics in the opposite direction, node by node perturbation , non-sustained perturbations (Deco et al., 2018;Perl, Escrichs, et al., 2021) or perturbing with external periodic force (Perl, Escrichs, et al., 2021;Perl, Pallavicini, et al., 2021). Notably, the perturbative approach allows for the exploration of brain responses elicited by in silico protocols which are not limited by ethical constraints of in vivo stimulations (Clausen, 2010;Kringelbach et al., 2007). Furthermore, the differential sensitivity of each brain state of external perturbations can serve as a specific biomarker that reveals features of their dynamical complexity. ...
Preprint
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Recently, significant advances have been made by identifying the levels of synchronicity of the underlying dynamics of a given brain state. This research has demonstrated that unconscious dynamics tend to be more synchronous than those found in conscious states, which are more asynchronous. Here we go beyond this dichotomy to demonstrate that the different brain states are always underpinned by spatiotemporal chaos but with dissociable turbulent dynamics. We investigated human neuroimaging data from different brain states (resting state, meditation, deep sleep, and disorders of consciousness after coma) and were able to distinguish between them using complementary model-free and model-based measures of turbulent information transmission. Our model-free approach used recent advances describing a measure of information cascade across spatial scales using tools from turbulence theory. Complementarily, our model-based approach used exhaustive in silico perturbations of whole-brain models fitted to the empirical neuroimaging data, which allowed us to study the information encoding capabilities of the brain states. Overall, the current framework demonstrates that different levels of turbulent dynamics are fundamental for describing and differentiating between brain states.
... Como todo procedimiento quirúrgico, no está exento de complicaciones, las cuales se pueden dividir en peri-operatorias, relacionadas con el hardware y efectos secundarios de la estimulación. En pacientes con enfermedad de Parkinson, donde se tiene más experiencia con esta técnica, las complicaciones peri-operatorias afectan aproximadamente a un 6,8% de los pacientes (Voges et al., 2007), siendo las más frecuente hemorragia (1.3-4%), y convulsiones (0.4-2.8%) (Clausen et al., 2010). Dentro de la segunda categoría, a saber, complicaciones relacionadas con el hardware, se encuentran infecciones (2.8-6.1%), ...
Article
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La estimulación cerebral profunda (DBS) es un procedimiento neuroquirúrgico usado actualmente para tratar síntomas motores de enfermedades como el Parkinson, distonías y el temblor esencial. Pero también se encuentra en desarrollo para apli-carse en el campo de la psiquiatría, por ejemplo, en las adicciones y trastornos de agresividad. Esto ha generado un importante debate a nivel bioético. Método: Se revisó la literatura buscando los problemas éticos que surgen de la aplicación de esta tecnología en dos patologías específicas, la enfermedad de Parkinson y el alcoholismo, haciendo énfasis sobre las implicancias que tiene sobre la libertad. Resultados: La DBS es una técnica en desarrollo con varios desafíos desde el punto de vista ético. Pero la mayoría de ellos se deben al hecho mismo de que se encuentra en desarrollo y con el tiempo deberían resolverse. Sin embargo, existen problemas particulares según el uso que se le dé a esta tecnología, los que se relacionan con la idea que tengamos sobre conceptos como la libertad. Conclusiónes: En el caso de la enfermedad de Parkinson nos parece un procedimiento aceptable desde el punto de vista ético, mientras que para trastornos como las adicciones su uso es discutible, y debiera usarse como terapia de segunda línea
... Inclusion criteria should aim to describe which patients are likely to benefit most from the intervention. By contrast, exclusion criteria can describe which patients are not likely to benefit from the treatment [45] or for whom the risks outweigh the potential benefits. Ideally, patients should have no serious medical comorbidities that could compromise DBS benefits or amplify surgical risk [43,46]. ...
Article
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Deep brain stimulation (DBS) is a neurosurgical treatment with a growing range of indications. The number of clinical studies is expanding because of DBS for new indications and efforts to improve DBS for existing indications. To date, various methods have been used to perform DBS studies. Designing a clinical intervention study with active implantable medical devices has specific challenges while expanding patient treatment. This paper provides an overview of the key aspects that are essential for setting up a DBS study.
... Associated hardware complications include skin erosions, lead migration, lead fracture/ failure, IPG malfunction, extension wire damage and failure of other electronic components [81]. Due to the highly complex nature of the surgery, care must be taken in the placement of electrodes, patient selection, IPG programming, postoperative stimulation, and drug-based treatment [82]. Errors in these areas can result in postoperative complications. ...
Article
Parkinson’s Disease (PD) is a neurodegenerative disorder that manifests as an impairment of motor and non-motor abilities due to a loss of dopamine input to deep brain structures. While there is presently no cure for PD, a variety of pharmacological and surgical therapeutic interventions have been developed to manage PD symptoms. This review explores the past, present and future outlooks of PD treatment, with particular attention paid to deep brain stimulation (DBS), the surgical procedure to deliver DBS, and its limitations. Finally, our group’s efforts with respect to brain mapping for DBS targeting will be discussed.
... 8 Even so, existing ethical frameworks often need to be applied to the specific context of neural device research and appropriately interpreted; additional guidance may be necessary. 5 Despite existing literature addressing the ethics of neural device research, especially deep brain stimulation (DBS), [9][10][11] further discussion and guidance on various ethics challenges is needed. 5 Considering these ethical challenges is also timely, as human studies will likely increase with advances in neuroscience. ...
Article
Importance Developing more and better diagnostic and therapeutic tools for central nervous system disorders is an ethical imperative. Human research with neural devices is important to this effort and a critical focus of the National Institutes of Health Brain Research Through Advancing Innovative Neurotechnologies (BRAIN) Initiative. Despite regulations and standard practices for conducting ethical research, researchers and others seek more guidance on how to ethically conduct neural device studies. This article draws on, reviews, specifies, and interprets existing ethical frameworks, literature, and subject matter expertise to address 3 specific ethical challenges in neural devices research: analysis of risk, informed consent, and posttrial responsibilities to research participants. Observations Research with humans proceeds after careful assessment of the risks and benefits. In assessing whether risks are justified by potential benefits in both invasive and noninvasive neural device research, the following categories of potential risks should be considered: those related to surgery, hardware, stimulation, research itself, privacy and security, and financial burdens. All 3 of the standard pillars of informed consent—disclosure, capacity, and voluntariness—raise challenges in neural device research. Among these challenges are the need to plan for appropriate disclosure of information about atypical and emerging risks of neural devices, a structured evaluation of capacity when that is in doubt, and preventing patients from feeling unduly pressured to participate. Researchers and funders should anticipate participants’ posttrial needs linked to study participation and take reasonable steps to facilitate continued access to neural devices that benefit participants. Possible mechanisms for doing so are explored here. Depending on the study, researchers and funders may have further posttrial responsibilities. Conclusions and Relevance This ethical analysis and points to consider may assist researchers, institutional review boards, funders, and others engaged in human neural device research.
Article
Bioelectronic medicine (BEM) offers exciting opportunities to treat diseases such as movement disorders and refractory inflammatory disease. The many variations of BEM allow for noninvasive aspects of treatment that might eliminate or reduce the need for pharmaceuticals; therefore, the term "electroceuticals" may be suitable. BEM has been effective for movement disorders and improvement of prosthetic devices. Based on this implication, there is an allowance to impact many focus areas that include but are not limited to autoimmune disease, sensory motor conditions, and neurological conditions. There are a wide array of ethical issues that relate to BEM, which include informed consent, research ethics, innovation, academic-industry relationships, intellectual property, and the conundrum that needs to be addressed when altering the brain such as the issues of autonomy and free beneficence and social justice. The major goal is to heighten awareness of ethical issues and facilitate a proactive ethical approach regarding BEM research.
Article
Background In recent years, qualitative changes in self-perception have been reported in individual patients undergoing brain stimulation to treat their neurological disease. We here report a first systematic study addressing these unwanted treatment effects in a semiquantitative way. Hypotheses Hypothesis 1 (H1): Changes in self-perception can be detected and documented in patients following interventions with various neurostimulating devices using standardized assessment tools. Hypothesis 2 (H2): Central nervous-implanted neurostimulating devices (deep brain stimulation [DBS]) will have a greater impact on the patient's self-perception than “peripheral” implanted devices (implanted vagus nerve stimulation [iVNS]) and external devices (transcutaneous vagus nerve stimulation [tVNS] or transcutaneous electrical trigeminal nerve stimulation [eTNS]). Methods Application of a newly developed semiquantitative questionnaire (FST-questionnaire [Fragebogen zur Veränderung der Selbstwahrnehmung unter tiefer Hirnstimulation]: Questionnaire regarding changes in self-perception while treated with DBS) to systematically assess changes in self-perception in a single-center, cross-sectional pilot-study at the University Hospital Freiburg, Germany on 50 patients (44% male; age 50 years [range: 27–73 years]), undergoing neurostimulation (DBS, iVNS, tVNS, or eTNS) to treat Parkinson's disease or epilepsy. Results Standardized assessment detected alterations in self-perception in all treatment groups (H1 approved). This included rare self-alienating changes in self-perception. Unexpectedly, peripheral neurostimulation had similar effects as central stimulation techniques. Conclusions Properly designed questionnaires – like the FST-questionnaire as standardized assessment tool – can detect changes in self-perception in patients during neurostimulatory treatment in a wide spectrum of brain stimulation techniques. This may provide a strategy to systematically identify the subgroup of patients liable to experience such problems during treatment already prior to treatment decisions.
Article
Objective: Discuss common clinical ethical challenges encountered in working with patients who are candidates for deep brain stimulation (DBS) for the treatment of motor symptoms of Parkinson's disease (PD). Method: The relevant literature is reviewed and supplemented by descriptive, ethically challenging cases stemming from decades of combined experience working on DBS teams. We outline ethical arguments and provide pragmatic recommendations to assist neuropsychologists working in movement disorder teams. Results: The goals of the pre-operative neuropsychological DBS assessment include: (1) identification of potential cognitive risk factors; (2) identification of relevant neuropsychiatric or neurobehavioral factors; (3) assessment of level of family support; and (4) systematic assessment of patient's and family member's goals or expectations for DBS. The information gleaned from the pre-operative neuropsychological assessment is highly relevant to the most commonly studied clinical ethics challenges encountered in DBS: (1) assessment of risk/benefit; (2) determinations regarding inclusion/exclusion; (3) autonomy; and (4) patient's perception of benefit and quality of life. Conclusions: Neuropsychologists are particularly well poised to provide unique and important insights to assist with developing the most ethically sound practices that take into account patient's values as well as fiduciary responsibilities to the patient, the team, the profession, and the broader community.
Article
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Deep brain stimulation has been of considerable interest to bioethicists, in large part because of the effects that the intervention can occasionally have on central features of the recipient’s personality. These effects raise questions regarding the philosophical concept of authenticity. In this article, we expand on our earlier work on the concept of authenticity in the context of deep brain stimulation by developing a diachronic, value-based account of authenticity. Our account draws on both existentialist and essentialist approaches to authenticity, and Laura Waddell Ekstrom’s coherentist approach to personal autonomy. In developing our account, we respond to Sven Nyholm and Elizabeth O’Neill’s synchronic approach to authenticity, and explain how the diachronic approach we defend can have practical utility, contrary to Alexandre Erler and Tony Hope’s criticism of autonomy-based approaches to authenticity. Having drawn a distinction between the authenticity of an individual’s traits and the authenticity of that person’s values, we consider how our conception of authenticity applies to the context of anorexia nervosa in comparison to other prominent accounts of authenticity. We conclude with some reflections on the prudential value of authenticity, and by highlighting how the language of authenticity can be invoked to justify covert forms of paternalism that run contrary to the value of individuality that seems to be at the heart of authenticity.
Chapter
A number of major national and international projects have recently been launched to meet the “Grand Challenge” of understanding the brain. With substantial funding, these projects aim to reveal the neurophysical processes underlying our mental states and seek to develop technologies to restore brain function when it has been impaired. The projects also include explicit investigation of the ethical, social, and legal implications of neuroscience and the ethical conduct of neuroscience research. The advent of these projects, therefore, offers an extraordinary opportunity for neuroethics to play an integral role in what may be the defining scientific program of our time. To fulfill this role, neuroethics must contribute fully to framing the investigation of ethical issues and the identification of those that need to be addressed. This chapter focuses on four issues that warrant particular attention as we move forward: (1) the ethical conduct of research; (2) responsible research and innovation; (3) responsibility, crime, and punishment; and (4) the identity of neuroethics.
Thesis
Die tiefe Hirnstimulation von Patienten, die unter Parkinson oder fokalen Epilepsien leiden, gilt als sicheres und wirksames Therapieverfahren. Einzelfallberichte und offene Interviews von Patienten, Angehörigen und Therapeuten haben aber eine Debatte über subtile Persönlichkeitsveränderungen als unerwünschte Nebenwirkung ausgelöst. In der vorliegenden Arbeit wurde ein erster Versuch unternommen diese qualitativen Hinweise auf subtile Persönlichkeitsveränderungen in dem Konstrukt Veränderungen der Selbstwahrnehmung zu quantifizieren. In einem ersten Schritt wurde auf Grundlage der rationalen Konstruktionsstrategie der FRAGEBOGEN ZUR VERÄNDERUNG DER SELBSTWAHRNEHMUNG UNTER TIEFER HIRNSTIMULATION (FST) mit 44 inhaltlichen Fragebogenitems entwickelt. Dieses Testinstrument wurde in einem zweiten Schritt eingesetzt um die der Arbeit zugrundeliegende Frage, ob Interventionen ins Gehirn – beispielsweise durch die Implantation eines elektrisch-technischen Gerätes (z.B. eines Tiefenhirnstimulators) – per se zu Veränderungen der Selbstwahrnehmung führen, quantitativ zu beantworten. In die explorative Testung des Fragebogen FST wurden 50 Patienten und 31 Angehörige eingeschlossen. Als Interventionsgruppe wurden Epilepsie- oder Parkinson-Patienten, die mit einem Tiefenhirnstimulator zentralnervös behandelt wurden, und als Kontrollgruppen Patienten, die mit einem Vagusnervstimulator oder mittels der Trigeminusnervstimulation peripher behandelt wurden, definiert. Die Ergebnisse zeigen, dass die Patienten mit allen Therapieverfahren zufriedenen sind. Bei der genaueren Interpretation der 27 „spezifischen“ Fragebogenitems, die sich explizit auf Veränderungen der Selbstwahrnehmung beziehen, zeigt sich aber, dass bei THS- und implantativen VNS-Patienten „mittelgradige“ Veränderungen der Selbstwahrnehmung stattfinden. Auch bei der Gruppe der Patienten, die mittels eines transkutanen Verfahren therapiert wurden, finden solche Veränderungen statt. Zwischen der Gruppe der THS-, der Gruppe der iVNS- und der Gruppe der TK-Patienten (tVNS-P und eTNS-P) konnte kein signifikanter Unterschied gezeigt werden, sodass die Annahme von Unterschieden zwischen den aus medizinischer Sicht zentralnervösen und peripheren oder zwischen den implantativen und transkutanen Stimulationsverfahren verworfen wurde. Die bei allen Patientengruppen vorhandenen (teilweise negativ konnotierten) Veränderungen der Selbstwahrnehmung lassen eine Untersuchung möglichst vieler neuromodulatorischer elektrisch-technischer Verfahren mittels des Fragebogen FST als sinnvoll erscheinen.
Article
Background Indications for deep brain stimulation (DBS) are rapidly growing within functional neurosurgery. The objective of this study was to characterize national trends in demographics and complications across distinct populations of DBS patients. Methods We identified patients from the 2008–2018 American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) Participant User File (PUF) who underwent an implantation or revision procedure for DBS. Summary statistics for postoperative infection rate, noninfectious complication rate, total hospital length of stay, discharge disposition, mortality, reoperation or readmission, and time from operation to readmission were obtained. Patients were categorized by diagnosis for DBS treatment. Outcomes for each diagnosis group were compared to outcomes for the total study population. Results DBS patients who underwent primary implantation procedures had low rates of postoperative infections (1.2%), noninfectious complications (0.8%), and mortality (0.1%) and a high likelihood of discharge home (97.6%). In addition, a large percentage of patients presented for revision or removal of neurostimulators (34.2% of cases) or treatment of long-term hardware infection (4.5%). Compared with patients with other diagnoses, patients with Parkinson disease experienced lower rates of noninfectious complications (OR 0.32; 95% CI, 0.15–0.63; p=0.002) and fewer unplanned reoperations (OR 0.60; 95% CI, 0.39–0.92; p=0.02). Conclusion Analysis of a national database suggests that DBS is a relatively safe treatment across several different patient populations. These overall favorable results support the continued practice of DBS surgery and provide encouraging validation for increasing access to DBS therapy for new indications that are being actively investigated.
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The idea of connecting a computer system to the human brain to enhance performance is no longer in the realm of science fiction. Invasive brain computer interfaces have medical and non-medical uses which can enhance the cognitive capacities of individuals, thereby enabling human beings to gain capabilities which otherwise would not have been possible. Consequently, the technology can enable individuals to flourish and pursue personal development in a manner of their choosing. However, unequitable access to invasive brain computer interfaces can create a cognitive gap and intelligence-asymmetry which can exacerbate the socio-economic inequalities by limiting the ability to access opportunities, economic and overall well-being of a person. Therefore, it is important to determine the extent of sufficiency of the existing primary law under the right to privacy which protects the right to human flourishing for effectively regulating and safeguarding the access to invasive brain computer interfaces.
Article
Background: Recent research suggests that a significant number of those who receive advanced treatments for Parkinson's disease (PD) do not report improvements for some symptoms, which may relate to their pre-treatment expectations. It is important that expectations of treatment are measured and discussed prior to advanced treatment. Objective: The primary aim of this study was to develop a measure of treatment expectations of two advanced-stage treatments in PD, deep brain stimulation (DBS), and Levodopa/Carbidopa Intestinal Gel (LCIG). A secondary aim was to explore potential predictors of treatment expectations. Methods: The questionnaire-based measure was developed by researchers in conjunction with a highly experienced clinician, and evaluated treatment expectations in 189 people aged 46-91 years (M = 71.35, SD = 8.73; 61% male) with idiopathic PD. Results: The overall measure demonstrated excellent internal consistency (α= 0.96). Exploratory factor analysis suggested the scale was unidimensional for both DBS and LCIG. Participant expectations of the two treatments differed significantly, with expectations being higher for DBS. Perceived symptom severity was the strongest predictor of treatment expectations. Conclusion: This scale has potential to inform clinicians about client expectations prior to advanced stage therapy for PD, with a view to the management of these expectations. Further evaluation of the scale is required across different treatment contexts.
Article
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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.
Chapter
The use of deep brain stimulation (DBS) as a therapy for neurological disorders, especially Parkinson’s disease (PD), is widely applied in the field of functional neurosurgery. Both the subthalamic nucleus and the globus pallidus interna are major targets for PD. Experimental DBS is performed using animal models to evaluate new indications and promote advancements in technology. In this chapter, we reviewed our experience with the concept of experimental DBS, including its development and validation. The following work aimed to establish that experimental DBS in animals is an adequate tool for exploring new indications for DBS and to further refine DBS technology.
Chapter
The development of neurotechnology and AI will provide enormous challenges for the legal system. Traditional criminal law is only partly adequate in regulating the development of neurotechnology and AI. The difficulties in assessing offender and victim or the relevant interests to be protected prove that criminalising in such contexts of new technologies with unclear responsibilities and unforeseeable developments is inadequate or even unjust. Therefore, a new balance of interests has to be found. This includes new ideas for (legal) obligations of patients using neurotechnology combined with AI, as this could potentially endanger others. Additionally, it will be important to reassess the border between the physical and mental sphere and re-evaluate legal protection of the latter—the importance of one’s identity and privacy has to be taken into account in the legal sphere more than it is done today. Also, we should reconsider the categories of “information”, “data” and “personal data” when it comes to neurotechnology. In times of Big Data, of AI combining the different information and deducing more information and, in many cases, even the identity of the person, these borders are difficult to uphold. The specific re-balancing of all interests involved has to be done by the legislator.
Book
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Cambridge Core - Social Psychology - Ethical Challenges in Digital Psychology and Cyberpsychology - by Thomas D. Parsons
Article
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The aims of this paper are to: (1) identify the best framework for comprehending multidimensional impact of deep brain stimulation (DBS) on the self; (2) identify weaknesses of this framework; (3) propose refinements to it; (4) in pursuing (3), show why and how this framework should be extended with additional moral aspects and demonstrate their interrelations; (5) define how moral aspects relate to the framework; (6) show the potential consequences of including moral aspects on evaluating DBS's impact on patients' selves. Regarding (1), I argue that the pattern theory of self (PTS) can be regarded as such a framework. In realizing (2) and (3), I indicate that most relevant issues concerning PTS that require resolutions are ontological issues, including the persistence question, the "specificity problem", and finding lacking relevant aspects of the self. In realizing (4), I identify aspects of the self not included in PTS which are desperately needed to investigate the full range of potentially relevant DBS-induced changes-authenticity, autonomy, and responsibility, and conclude that how we define authenticity will have implications for our concept of autonomy, which in turn will determine how we think about responsibility. Concerning (5), I discuss a complex relation between moral aspects and PTS-on one hand, they serve as the lens through which a particular self-pattern can be evaluated; on the other, they are, themselves, products of dynamical interactions of various self-aspects. Finally, I discuss (6), demonstrating novel way of understanding the effects of DBS on patients' selves.
Article
Dystonia is a movement disorder that can have a debilitating impact on motor functions and quality of life. There are 250,000 cases in the United States, most with childhood onset. Due to the limited effectiveness and side effects of available treatments, pediatric deep brain stimulation (pDBS) has emerged as an intervention for refractory dystonia. However, there is limited clinical and neuroethics research in this area of clinical practice. This paper examines whether it is ethically justified to offer pDBS to children with refractory dystonia. Given the favorable risk-benefit profile, it is concluded that offering pDBS is ethically justified for certain etiologies of dystonia, but it is less clear for others. In addition, various ethical and policy concerns are discussed, which need to be addressed to optimize the practice of offering pDBS for dystonia. Strategies are proposed to help address these concerns as pDBS continues to expand.
Chapter
Ethics in Neurosurgical Practice - edited by Stephen Honeybul June 2020
Book
Cambridge Core - Neurology and Clinical Neuroscience - Ethics in Neurosurgical Practice - edited by Stephen Honeybul
Chapter
As a treatment approved and certified for certain neurological diseases, deep brain stimulation (DBS) sometimes produces spectacular results quickly. It is also a powerful research tool in neurology and psychiatry. It combines a highly technical surgical procedure with a complex active medical device that acts on the brain, the substratum of human thought and identity. It raises several ethical and legal questions. Some are not specific, and can be solved by applying the principles of medical ethics and law. Others appear to be more DBS-specific. Some arise from the intrication of research and treatment in its development, and from the need to tune the device. Some are related to its effectiveness and its occasional harmful side effects (including potential applications beyond the field of health care).
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Deep brain stimulation (DBS) is an approved treatment for neurological diseases and a promising one for psychiatric conditions, which may produce spectacular results very quickly. It is also a powerful tool for brain research and exploration. Beyond an overview of the ethical and legal literature on this topic, this paper aims at showing that DBS is a compelling example for ethical-legal reflection, as it combines a highly technical surgical procedure, a complex active medical device and neuromodulation of the human brain to restore lost abilities caused by a chronic and evolving disease. Some of the ethical and legal issues raised by DBS are not specific, but shed new light on medical ethics and law. Others are more DBS-specific, as they are linked to the intricacies of research and treatment, to the need to tune the device, to the patients’ control over the device and its effects and to the involvement of family caregivers.
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The phenomenological effects of deep brain stimulation (DBS) on the self of the patient remains poorly understood and under described in the literature, despite growing evidence that a significant number of patients experience postoperative neuropsychiatric changes. To address this lack of phenomenological evidence, we conducted in-depth, semistructured interviews with 17 patients with Parkinson's disease who had undergone DBS. Exploring the subjective character specific to patients' experience of being implanted gives empirical and conceptual understanding of the potential phenomenon of DBS-induced self-estrangement. Our study concluded that (1) the more patients preoperatively felt alienated by their illness, the more they experienced postoperative self-estrangement, and (2) the notion of self-estrangement seems to exist in association with certain common qualitative characters, namely, loss of control, which reflects a deteriorative estrangement, and distorted perception of capacities, which reveals a restorative estrangement. These findings indicate that subjective self-reports help us to understand some aspects of the potential phenomenon of DBS-induced self-estrangement.
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Background In many patients with idiopathic Parkinson's disease, treatment with levodopa is complicated by fluctuations between an “off” period (also referred to as “off medication”), when the medication is not working and the motor symptoms of parkinsonism are present, and an “on” period, when the medication is causing improved mobility (also referred to as “on medication”), often accompanied by debilitating dyskinesias. In animal models of Parkinson's disease, there is overactivity in the subthalamic nucleus, and electrical stimulation of the subthalamic nucleus improves parkinsonism. We therefore sought to determine the efficacy and safety of electrical stimulation of the subthalamic nucleus in patients with Parkinson's disease. Methods We studied 24 patients with idiopathic Parkinson's disease in whom electrodes were implanted bilaterally in the subthalamic nucleus under stereotactic guidance with imaging and electrophysiologic testing of the location. Twenty were followed for at least 12 months. Clinical evaluations included the Unified Parkinson's Disease Rating Scale, a dyskinesia scale, and timed tests conducted before and after surgery, when patients were off and on medications. Results After one year of electrical stimulation of the subthalamic nucleus, the patients' scores for activities of daily living and motor examination scores (Unified Parkinson's Disease Rating Scale parts II and III, respectively) off medication improved by 60 percent (P<0.001). The subscores improved for limb akinesia, rigidity, tremor, and gait. In the testing done on medication, the scores on part III improved by 10 percent (P<0.005). The mean dose of dopaminergic drugs was reduced by half. The cognitive-performance scores remained unchanged, but one patient had paralysis and aphasia after an intracerebral hematoma during the implantation procedure. Conclusions Electrical stimulation of the subthalamic nucleus is an effective treatment for advanced Parkinson's disease. The severity of symptoms off medication decreases, and the dose of levodopa can be reduced, with a consequent reduction in dyskinesias.
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The preceding decade has witnessed tremendous progress in clinical as well as theoretical neuroscience. In its wake, powerful new instruments of neuromodulation acting directly on the brain have been developed: potent neuro-pharmaceuticals, deep brain stimulation, transcranial magnetic stimulation, various methods of neurotransplantation, central neural prostheses, and others. However, few areas of scientific development seem to exhibit as close a connection between dreams of progress and nightmares of disaster as contemporary neuroscience. This Janus-faced character relates to the core function of the brain as the "organ of the mind". Methods of intervening in the brain easily draw the suspicion of possibly altering fundamental features of personhood, thus posing a threat to preconditions of human dignity and to the normative structure of our societies. This suspicion has been fuelled by the discovery that most of the newly developed neurotherapeutic instruments might also be used for purposes of enhancement of certain mental features. "Mind doping" is a populist slogan at hand, suggesting a deprecatory parallel to the practice of doping in sports. The present book subjects the whole range of questions associated with these problems to a thorough exploration. Extensive state-of-the-art accounts of the relevant clinical and theoretical neurosciences are followed by an in-depth philosophical analysis of the problems of personal identity and a comprehensive disquisition on legal and ethical questions posed by present and foreseeable future practices of neuroenhancement. A concluding chapter presents the study’s main results as recommendations, addressing clinical practitioners and researchers in the field as well as to politicians, legislators, law courts, philosophers, lawyers, and anybody fascinated by or concerned about the dawning era of intervening in the brain.
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Major depression is the most common serious brain disorder with a lifetime prevalence of up to 17%. Despite numerous options currently available for the treatment of depression, ~2 million people in the United States may experience an inadequate response to treatment (treatment-resistant depression [TRD]) at some point in their lives. The definition of TRD is variable, ranging from a failure to respond to two or more trials of antidepressant monotherapy to a failure to respond to four or more trials of different antidepressant therapies, including augmentation, combination therapy, and electroconvulsive therapy. It has been reported that as many as one-third of patients experience only a partial response to initial therapy, while nearly one-fifth are considered nonresponders. In addition to the obvious quality of life issues for the patient with TRD, the economic cost of TRD is significant. Annual healthcare costs increase significantly for patients with TRD with each successive change in antidepressant medication. Early in treatment (two medication changes), the annual costs are <$7,000/Year. By the eighth medication change, annual costs double to nearly $14,000/year. There is a well-documented need for better long-term treatments for TRD, as witnessed by multiple efforts to establish treatment algorithms and best treatment steps when first and subsequent treatment measures prove inadequate. The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, which analyzed outcome following several standardized antidepressive treatment steps, reported that 33% of patients did not respond even after four evidence-based treatment steps. A substantial proportion of patients are inadequately treated and some of these will go on to suffer from chronic, debilitating, and life-threatening symptoms.
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Deep brain stimulation (DBS), an established treatment for some movement disorders, is now being used experimentally to treat psychiatric disorders as well. In a number of recently published case series, DBS yielded an impressive therapeutic benefit in patients with medically intractable psychiatric diseases. This review of the use of DBS to treat psychiatric disorders is based on literature retrieved from a selective Pubmed search for relevant keywords, reference works on the topic, and the authors' own research. Studies have been performed on the use of DBS to treat medically intractable obsessive-compulsive disorder, depressive disorders, and Tourette syndrome. The case numbers in the cited publications were small, yet at least some of them involved a methodologically sound investigation. Thus, in some studies, the strength of the effect was controlled with a double-blinded interval in which the stimulation was turned off. In general, the primary symptoms were found to improve markedly, by 35% to 70%, although not all patients responded to the treatment. Adverse effects of DBS were very rare in most studies and could usually be reversed by changing the stimulation parameters. The results of DBS for psychiatric disorders that have been published to date are encouraging. They open up a new perspective in the treatment of otherwise intractable disorders. Nonetheless, the efficacy, mechanism of action, and adverse effects of DBS for this indication still need to be further studied in methodologically adequate trials that meet the highest ethical standard.
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Chittaranjan Andrade (India), Andreas Conca (Austria), Delcir da Costa (Brazil), Gerhard Eschweiler (Germany), Max Fink (USA), Paul Fitzgerald (Australia), Loes Gabriels (Belgium), Christian Geretsegger (Austria), Benjamin Greenberg (USA), Paul Holtzheimer (USA), Mindaugas Jasulaitis (Lithuania), Andy Krystal (USA), Yechiel Levkovitz (Israel), Daniel Lijtenstein (Uruguay), Sarah H. Lisanby (USA), Philip Mitchell (Australia), Nobutaka Motohashi (Japan), Angela Naderi-Heiden (Austria), Jose Otegui (Uruguay), Harold Sackeim (USA), E. Tsukarzi (Russia), Ioannis Zervas (Greece).
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Introduction Major depressive disorder is one of the most disabling and common diagnoses amongst psychiatric disorders, with a current worldwide prevalence of 5–10% of the general population and up to 20–25% for the lifetime period. Historical perspective Nowadays, conventional treatment includes psychotherapy and pharmacotherapy; however, more than 60% of the treated patients respond unsatisfactorily, and almost one fifth becomes refractory to these therapies at long-term follow-up. Nonpharmacological techniques Growing social incapacity and economic burdens make the medical community strive for better therapies, with fewer complications. Various nonpharmacological techniques like electroconvulsive therapy, vagus nerve stimulation, transcranial magnetic stimulation, lesion surgery, and deep brain stimulation have been developed for this purpose. Discussion We reviewed the literature from the beginning of the twentieth century until July 2009 and described the early clinical effects and main reported complications of these methods.
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Treatment of alcohol dependence remains one of the biggest challenges in psychiatry, since only about half of all patients achieve long-term abstinence by the currently available therapies. Dysfunction of the nucleus accumbens, one of the main areas of the brain's reward system, seems to play a central role in addiction and treatment resistance. Following the recent advances of neuromodulation therapy by deep brain stimulation, we designed an off-label single patient study protocol to treat patients with severe and long-standing alcoholism in whom other treatment options had failed. We report here on the first three patients with alcoholism who received deep brain stimulation. In the one-year follow-up period, two remained abstinent, while one showed a remarkable reduction of days while drinking and none had any significant adverse effects.
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Psychiatric neurosurgery, specifically stereotactic ablation, has continued since the 1940s, mainly at a few centers in Europe and the US. Since the late 1990s, the resurgence of interest in this field has been remarkable; reports of both lesion procedures and the newer technique of deep brain stimulation (DBS) have increased rapidly. In early 2009, the US FDA granted limited humanitarian approval for DBS for otherwise intractable obsessive-compulsive disorder (OCD), the first such approval for a psychiatric illness. Several factors explain the emergence of DBS and continued small-scale use of refined lesion procedures. DBS and stereotactic ablation have been successful and widely used for movement disorders. There remains an unmet clinical need: current drug and behavioral treatments offer limited benefit to some seriously ill people. Understandings of the neurocircuitry underlying psychopathology and the response to treatment, while still works in progress, are much enhanced. Here, we review modern lesion procedures and DBS for OCD in the context of neurocircuitry. A key issue is that clinical benefit can be obtained after surgeries targeting different brain structures. This fits well with anatomical models, in which circuits connecting orbitofrontal cortex (OFC), medial prefrontal cortex (mPFC), basal ganglia, and thalamus are central to OCD pathophysiology and treatment response. As in movement disorders, dedicated interdisciplinary teams, here led by psychiatrists, are required to implement these procedures and maintain care for patients so treated. Available data, although limited, support the promise of stereotactic ablation or DBS in carefully selected patients. Benefit in such cases appears not to be confined to obsessions and compulsions, but includes changes in affective state. Caution is imperative, and key issues in long-term management of psychiatric neurosurgery patients deserve focused attention. DBS and contemporary ablation also present different patterns of potential benefits and burdens. Translational research to elucidate how targeting specific nodes in putative OCD circuitry might lead to therapeutic gains is accelerating in tandem with clinical use.
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Advanced Parkinson's disease (PD) is associated with various motor and non-motor symptoms which adversely impact health-related quality of life (HRQoL). Subthalamic nucleus (STN) deep brain stimulation (DBS) has been reported to improve some dimensions of HRQoL in appropriately selected candidates. Prior studies of HRQoL following DBS have used instruments comprising a predetermined list of questions which assess issues that are generally relevant in PD, but that may not be of equal or consistent importance to all individuals. In this study, we evaluate the effect of STN DBS on quality of life using the QLS(M), a modular questionnaire in which satisfaction scores for each item are weighted in light of patient-rated importance. We prospectively analysed QLS(M) scores in 21 patients with PD (11 men, mean age 61.5+/-8.6 years) before STN DBS surgery and at a mean 7.4+/-1.5, and again at a mean 16.6+/-6.8 months postoperatively. Following STN DBS, patients experienced an improvement in HRQoL as measured by various items of the movement disorder and health modules of the QLS(M). Specifically, QLS(M) items pertaining to energy level/enjoyment of life, independence from help, controllability/fluidity of movement and steadiness when standing and walking showed significant improvements, although items concerning general life issues (eg, occupational function, interpersonal relationships, leisure activities) did not improve. Following STN DBS, symptomatic and functional improvements translate into higher HRQoL, with high satisfaction in domains related to movement disorders and general health.
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At the height of the psychosurgery debate the editors of The Lancet referenced the popular hesitancy to intervene surgically with the workings of the brain. They wrote that to do so `carries a peculiar penumbra of sacrilege' [1, 2]. Penumbra of sacrilege is a memorable, even strange phrase. It is one worth unpacking as we embark on an era which will see ever more border crossings at the blood-brain barrier. By invoking popular beliefs about a penumbra of sacrilege, the editors were suggesting that psychosurgery represented a gray zone in the shadows, a desecration or violation of a sacred space, the seat of the soul, the self. And as such, they were reflecting a cultural hesitancy, a lay reluctance to pursue this work. Fortunately for those with intractable neuropsychiatric disorders, neuromodulation has evolved beyond the primitive---and barbaric---sweep of the lobotomy, and with this advance, categorical resistance to this work has dissipated. And that is all to the good. But as the field progresses, and we implant more and more devices for therapeutic and investigational purposes, we must not let the placement of electrodes become too easy. It is a decision that should be made with full awareness of its implications for patients and families. Recently, I spoke to a friend who appeared to have early essential tremor. (Some non-essential aspects of this story have been changed to protect confidentiality.) He asked me, `Do you know anything about deep brain stimulation?' I indicated that I did. `Really?', he asked, seemingly unaware of my scholarly interest in the topic [3, 4, 5, 6] and involvement as a co-investigator in the use of deep brain stimulation in the minimally conscious state [7, 8, 9]. Satisfied that I might be a credible source for some free advice, he told me that his neurologist had sent him to a neurosurgeon to see about a stimulator. I asked him how disabling his condition was. As he competently drank a cup of soda, he told me it was a bit of a nuisance but nothing worse. As I recall the conversation, he was not receiving much more than a low-dose beta-blocker by way of medical management. Although I am an internist, and neither a neurologist nor neurosurgeon, it struck me as a bit premature to shuttle my friend off for an implant. It just should not be so easy. I asked myself: where had that penumbra of sacrilege gone? At some level, has this gotten too easy, too routine? Although this is but an anecdote, it is a disturbing one. My friend's referral was outside coverage norms established by the Centers for Medicare & Medicaid Services (CMS). Their 2003 national coverage determination for thalamic ventralis intemedius nucleus (VIM) deep brain stimulation (DBS) in essential tremor requires `marked disabling tremor of at least level 3 or 4 on the Fahn-Tolosa-Marin tremor rating scale (or equivalent scale) in the extremity intended for treatment, causing significant limitation in daily activities despite optimal medical therapy' [10, 11]. As best as I could tell, my friend met neither criteria for symptom severity nor adequate medical treatment. Even more striking was the casualness with which he told me about his neurologist's referral. One would think that he was being sent for the simplest of procedures, without any risks or long-term sequelae, notwithstanding specific complications associated with thalamic DBS for essential tremor [12]. It is a tribute to the nascent field of neuromodulation that, in the twenty years since Professor Alim Benabid's pioneering work heralded these new treatment modalities [13], stimulator placement has been analogized to the insertion of a heart pacemaker. But is the insertion of a cerebral pacemaker as routine as its cardiac counterpart? At this juncture I would venture to say it is not. While the acute surgical risks are slim, the longitudinal challenge for competent on-going care is high. Simply put, the community-based infrastructure to follow and support the growing number of patients with deep brain stimulators does not exist. Most patients go to highly specialized centers that have interdisciplinary teams able to assess, implant and support patients. But after surgery they return to their communities only to find a paucity of qualified neurologists and neurosurgeons able to provide on-going care. Even for rather routine matters like battery replacement or the adjustment of stimulation parameters, they need to return to the centers that performed the surgery. Follow-up there is all the more necessary for hardware failures, which still occur at non-trivial rates [14, 15]. This dependence on the mother ship is not the same for cardiac pacemakers. Any community hospital with a cardiology service can handle most complications and provide routine maintenance. Until a comparable neuromodulation infrastructure is in place, we need to be more prudent in determining who gets a stimulator. The prospects are even worse for those who are enrolled in clinical trials for new indications or have an innovative investigational device. What is their fate? What happens to these patients when the trial ends? Who provides on-going care? Who pays for battery replacement? Who removes a broken device? Who adjusts stimulation parameters ... in perpetuity? Because there is still virtually no group to take on these tasks, it is critically important that the neuromodulation community collectively affirm our on-going ethical obligation to these subjects once they leave trials and become patients. Our professional norms should reflect adherence to the ethical principle of non-abandonment. This duty is grounded in a deontological respect for persons. In the context of a neuromodulation trial, this means that once a subject is enrolled in a trial or under our care, we have a longitudinal fiduciary obligation to provide them with support. After a subject is implanted, the investigative team---and its sponsors---incur a clinical responsibility to provide on-going care and a fiscal responsibility for any associated costs. It is a breach of professional ethics to do otherwise. Such enduring covenants must be articulated in clinical protocols and be determinative in regulatory decisions by local Institutional Review Boards (IRBs) to reject or approve investigative protocols. The articulation of such `after-care' provisions should also be expected in any new IDE application to the Food and Drug Administration. To sustain clinical progress and investigative momentum, the neuromodulation community must embrace its ethical responsibility for comprehensive and on-going follow-up care. We need to populate a clinical infrastructure that can support patients and research subjects in their communities, especially as their conditions deteriorate and travel becomes more difficult. We need to disseminate our sequestered expertise more widely to primary care specialties. This ethical mandate transcends the clinical assessors, operators, and sponsors of clinical trials. It also applies to engineers who are well-positioned to help lessen the burden for patients and subjects. On the engineering side of this equation, innovation is the key. The development of better batteries with longer shelf lives or power management systems that optimize utilization of available capacitance will be a tremendous boon in streamlining follow-up care. So too will be the development of simplified device control systems to manipulate basic functions that would be operable by generalist physicians. Imagine a universal wand that could deactivate a device, and perform some rudimentary functions, that every Emergency Department could stock. Making such a basic parallel low-tech system universal amongst many device manufacturers would provide additional access to care in the community and a degree of safety in an emergency. Engineers might also work towards the development of mechanisms to give patients and subjects greater control over their devices, which are after all extrinsic intrusions on their bodies and their selves. Previously, I suggested that stimulation parameters for the treatment of neuropsychiatric disorders might be manipulated by patients one day. I envisioned a degree of patient discretion, within a pre-set safe range determined by physicians, much like patient-controlled analgesia (PCA) pumps give patients control over the dosing of opioid analgesia [3]. I am glad that such an advance is evolving as a means to preserve batteries in the treatment of motor disorders [16]. I would encourage the neural engineers to embrace the ethical mandate to develop additional platforms that might enhance patient self-determination and foster a greater degree of functional independence. While the neuromodulation community has every reason to celebrate its accomplishments, it would be better served by appreciating that the insertion of a device into the human brain comes with, if not the penumbra of sacrilege, a moral obligation to step out of the shadows and remain clearly available to patients and families over the long haul. Although neuromodulation has liberated many patients from the shackles of disease, we need to appreciate that the hardware that has made this possible can remain tethering. The challenge for the next generation of innovators is to minimize these burdens at this neural interface. By reducing barriers to care that exist in an unprepared health care system and developing more user-friendly technology, the neuromodulation community can expand its reach and broaden the relief provided by these neuro-palliative interventions [17]. Acknowledgements and Disclosures Dr Fins is the recipient of an Investigator Award in Health Policy Research (Minds Apart: Severe Brain Injury and Health Policy) from The Robert Wood Johnson Foundation. He also gratefully acknowledges grant support from the Buster Foundation (Neuroethics and Disorders of Consciousness). He is an unfunded co-investigator of a study of deep brain stimulation in the minimally conscious state, funded by Intelect Medical Inc. References [1] 1972 Editorial: Psychosurgery Lancet 7767 69-70 [2] Fins J J 2002 The ethical limits of neuroscience The Lancet Neurology 1 213 [3] Fins J J 2003 From psychosurgery to neuromodulation and palliation: history's lessons for the ethical conduct and regulation of neuropsychiatric research Neurosurgery Clinics of North America 14 303-19 [4] Fins J J 2004 Deep brain stimulation Encyclopedia of Bioethics, Vol 2 3rd edn, ed S G Post (New York: MacMillan Reference) pp 629-34 [5] Fins J J 2004 Neuromodulation, free will and determinism: lessons from the psychosurgery debate Clinical Neuroscience Research 4 113-18 [6] Fins J J 2009 Deep brain stimulation: ethical issues in clinical practice and neurosurgical research Neuromodulation eds E Krames, P H Peckham and A Rezai (London: Elsevier) pp 81-91 [7] Schiff N D, Giacino J T, Kalmar K, Victor J D, Baker K, Gerber M, Fritz B, Eisenberg B, O'Connor J, Kobylarz E J, Farris S, Machado A, McCagg C, Plum F, Fins J J, Rezai A R 2007 Behavioral improvements with thalamic stimulation after severe traumatic brain injury Nature 448 600-3 [8] Schiff N D and Fins J J 2007 Deep brain stimulation and cognition: moving from animal to patient Current Opinion in Neurology 20 638-42 [9] Schiff N D, Giacino J T and Fins J J 2009 Deep brain stimulation, neuroethics and the minimally conscious state: moving beyond proof of principle Arch. Neurology 66 697-702 [10] CMS 160.24 NCD for deep brain stimulation for essential tremor and Parkinson's disease, 1~April~2003 [11] CMS Manual System 100-04 Medicare claims processing, transmittal 128, 26 March 2004 http://www.cms.hhs.gov/Transmittals/Downloads/R128CP.pdf [12] Schwalb J M, Riina H A, Skolnick B, Jaggi J L, Simuni T and Baltuch G H 2001 Revision of deep brain stimulator for tremor: technical note J. Neurosurg. 94 1010-12 [13] Speelman J D and Bosch D A 1998 Resurgence of functional neurosurgery for Parkinson's disease: a historical perspective Movement Disorders 13 582-8 [14] Kondziolka D, Whiting D, Germanwala A and Oh M 2002 Hardware-related complications after placemen of thalamic deep brain stimulator systems Stereotact. Funct. Neurosurg. 79 228-33 [15] Okun M S, Tagliati M, Pourfar M, Fernandez H H, Rodriguez R L, Alterman R L and Foote K~D 2005 Management of referred deep brain stimulation failures: a retrospective analysis from movement disorders centers Arch. Neurology 62 1250-5 [16] Kronenbuerger M, Fromm C, Block F, Coenen V A, Rohde I, Rohde V and Noth J 2006 On-demand deep brain stimulation for essential tremor: a report on four cases Movement Disorders 21 401-5 [17] Fins J J 2008 Neuroethics and disorders of consciousness: a pragmatic approach to neuro-palliative care The Neurology of Consciousness, Cognitive Neuroscience and Neuropathology eds S Laureys and G Tononi (New York: Academic-Elsevier) pp 234-44
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Brain-implantable devices have a promising future. Key safety issues must be resolved, but the ethics of this new technology present few totally new challenges, says Jens Clausen.
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In many patients with idiopathic Parkinson's disease, treatment with levodopa is complicated by fluctuations between an "off" period, when the medication is not working and the motor symptoms of parkinsonism are present, and an "on" period, when the medication is causing improved mobility, often accompanied by debilitating dyskinesias. In animal models of Parkinson's disease, there is overactivity in the subthalamic nucleus, and electrical stimulation of the subthalamic nucleus improves parkinsonism. We therefore sought to determine the efficacy and safety of electrical stimulation of the subthalamic nucleus in patients with Parkinson's disease. We studied 24 patients with idiopathic Parkinson's disease in whom electrodes were implanted bilaterally in the subthalamic nucleus under stereotactic guidance with imaging and electrophysiologic testing of the location. Twenty were followed for at least 12 months. Clinical evaluations included the Unified Parkinson's Disease Rating Scale, a dyskinesia scale, and timed tests conducted before and after surgery, when patients were off and on medications. After one year of electrical stimulation of the subthalamic nucleus, the patients' scores for activities of daily living and motor examination scores (Unified Parkinson's Disease Rating Scale parts II and III, respectively) off medication improved by 60 percent (P<0.001). The subscores improved for limb akinesia, rigidity, tremor, and gait. In the testing done on medication, the scores on part III improved by 10 percent (P<0.005). The mean dose of dopaminergic drugs was reduced by half. The cognitive-performance scores remained unchanged, but one patient had paralysis and aphasia after an intracerebral hematoma during the implantation procedure. Electrical stimulation of the subthalamic nucleus is an effective treatment for advanced Parkinson's disease. The severity of symptoms off medication decreases, and the dose of levodopa can be reduced with consequent reduction in dyskinesias.
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Background Although the short-term benefits of bilateral stimulation of the subthalamic nucleus in patients with advanced Parkinson's disease have been well documented, the long-term outcomes of the procedure are unknown. Methods We conducted a five-year prospective study of the first 49 consecutive patients whom we treated with bilateral stimulation of the subthalamic nucleus. Patients were assessed at one, three, and five years with levodopa (on medication) and without levodopa (off medication), with use of the Unified Parkinson's Disease Rating Scale. Seven patients did not complete the study: three died, and four were lost to follow-up. Results As compared with base line, the patients' scores at five years for motor function while off medication improved by 54 percent (P<0.001) and those for activities of daily living improved by 49 percent (P<0.001). Speech was the only motor function for which off-medication scores did not improve. The scores for motor function on medication did not improve one year after surgery, except for the dyskinesia scores. On-medication akinesia, speech, postural stability, and freezing of gait worsened between year 1 and year 5 (P<0.001 for all comparisons). At five years, the dose of dopaminergic treatment and the duration and severity of levodopa-induced dyskinesia were reduced, as compared with base line (P<0.001 for each comparison). The average scores for cognitive performance remained unchanged, but dementia developed in three patients after three years. Mean depression scores remained unchanged. Severe adverse events included a large intracerebral hemorrhage in one patient. One patient committed suicide. Conclusions Patients with advanced Parkinson's disease who were treated with bilateral stimulation of the subthalamic nucleus had marked improvements over five years in motor function while off medication and in dyskinesia while on medication. There was no control group, but worsening of akinesia, speech, postural stability, freezing of gait, and cognitive function between the first and the fifth year is consistent with the natural history of Parkinson's disease.
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Frontal leucotomy, despite certain limitations of the operative method, must be considered one of the most important discoveries ever made in psychiatric therapy, because through its use a great number of suffering people and total invalids have recovered and have been socially rehabilitated.
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In 1992 the Core Assessment Program for Intracerebral Transplantations (CAPIT) was published providing the minimal requirements for a common patient evaluation protocol. Despite the intent, the program was thought to be too laborious to carry out in large scale trials, and it also lacked evaluations of cognitive functions and quality of life. Moreover, the CAPIT was designed for neural transplantation only and has not been revised since. Since then, pallidotomy and deep brain stimulation have emerged as additional treatment modalities but there exists no common tool for evaluation of, and between, the techniques. In 1996, within the framework of NECTAR (Network for European CNS Transplantation and Restoration), a dedicated program entitled “Neurosurgical Interventions in Parkinson's Disease” (NIPD) was funded by the European Union Biomed 2 program to develop a new Core Assessment Program for Surgical Interventional Therapies in PD (CAPSIT-PD) and to establish an European registry for patients with PD subjected to functional neurosurgery. This article presents the recommendations of this new program.
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Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor, cognitive, neuropsychiatric, autonomic, and other nonmotor symptoms. The efficacy of deep brain stimulation (DBS) for the motor symptoms of advanced PD is well established. However, the effects of DBS on the cognitive and neuropsychiatric symptoms are less clear. The neuropsychiatric aspects of DBS for PD have recently been of considerable clinical and pathophysiological interest. As a companion to the preoperative and postoperative sections of the DBS consensus articles, this article reviews the published literature on the cognitive and neuropsychiatric aspects of DBS for PD. The majority of the observed neuropsychiatric symptoms are transient, treatable, and potentially preventable. Outcome studies, methodological issues, pathophysiology, and preoperative and postoperative management of the cognitive and neuropsychiatric aspects and complications of DBS for PD are discussed. © 2006 Movement Disorder Society
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Despite the overall excellent outcome of neurosurgery in patients with Parkinson’s disease, there is often a contrast between the improvement in motor disability and the difficulties of patients to reintegrate a normal life. In this study, the personal, familial and professional difficulties experienced by patients two years after bilateral high frequency stimulation of the subthalamic nucleus were carefully analyzed. To avoid such socio-familial maladjustment, we strongly suggest taking into consideration the patients’ psychological and social context before the operation and during the post-operative follow-up.
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A preliminary report in six patients suggested that deep brain stimulation (DBS) of the subcallosal cingulate gyrus (SCG) may provide benefit in treatment-resistant depression (TRD). We now report the results of these and an additional 14 patients with extended follow-up. Twenty patients with TRD underwent serial assessments before and after SCG DBS. We determined the percentage of patients who achieved a response (50% or greater reduction in the 17-item Hamilton Rating Scale for Depression [HRSD-17]) or remission (scores of 7 or less) after surgery. We also examined changes in brain metabolism associated with DBS, using positron emission tomography. There were both early and progressive benefits to DBS. One month after surgery, 35% of patients met criteria for response with 10% of patients in remission. Six months after surgery, 60% of patients were responders and 35% met criteria for remission, benefits that were largely maintained at 12 months. Deep brain stimulation therapy was associated with specific changes in the metabolic activity localized to cortical and limbic circuits implicated in the pathogenesis of depression. The number of serious adverse effects was small with no patient experiencing permanent deficits. This study suggests that DBS is relatively safe and provides significant improvement in patients with TRD. Subcallosal cingulate gyrus DBS likely acts by modulating brain networks whose dysfunction leads to depression. The procedure is well tolerated and benefits are sustained for at least 1 year. A careful double-blind appraisal is required before the procedure can be recommended for use on a wider scale.
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Neurostimulation to restore cognitive and physical functions is an innovative and promising technique for treating patients with severe brain injury that has resulted in a minimally conscious state (MCS). The technique may involve electrical stimulation of the central thalamus, which has extensive projections to the cerebral cortex. Yet it is unclear whether an improvement in neurological functions would result in a net benefit for these patients. Quality-of-life measurements would be necessary to determine whether any benefit of neurostimulation outweighed any harm in their response to different degrees of cognitive and physical disability. These measures could also indicate whether the technique could be ethically justified and whether surrogates could give proxy consent to its use on brain-injured patients.
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Chronic consumption of alcohol represents one of the greatest health and socioeconomic problems worldwide. We report on a 54-year-old patient with a severe anxiety disorder and secondary depressive disorder in whom bilateral deep brain stimulation (DBS) of the nucleus accumbens was carried out. Despite the absence of desired improvement in his primary disorder, we observed a remarkable although not primarily intended alleviation of the patient's comorbid alcohol dependency. Our case report demonstrates the extremely effective treatment of alcohol dependency by means of DBS of the nucleus accumbens and may reveal new prospects in overcoming therapy resistance in dependencies in general.
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In 2004, the International Committee of Medical Journal Editors put forward a fundamental truth: “The case against selective reporting is particularly compelling for research that tests interventions that could enter mainstream clinical practice.”1 There is perhaps no arena in medical research where the threat of selective reporting is greater than in the emerging field of deep brain stimulation (DBS) and neuromodulation. This intervention is now being studied2 for the treatment of several psychiatric diseases such as treatment-refractory obsessive-compulsive disorder, major depression, and Tourette syndrome as well as behavioral conditions like obesity, violent behavior, and substance abuse.
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Deep brain stimulation (DBS) has been increasingly utilized for the therapeutic treatment of movement disorders, and with the advent of this therapy more postoperative urgencies and emergencies have emerged. In this paper, we will review, identify, and suggest management strategies for both intra- and postoperative urgencies and emergencies. We have separated the scenarios into 1--surgery/procedure related, 2--hardware related, 3--stimulation-induced difficulties, and 4--others. We have included ten illustrative (and actual) case vignettes to augment the discussion of each issue.
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Deep brain stimulation (DBS) is an established treatment option for some movement disorders, in particular Parkinson's disease. Only recently, a number of promising studies with small samples of patients have been published in which impressive therapeutic outcomes achieved by DBS in otherwise treatment-resistant obsessive-compulsive disorder, major depression, and Tourette's syndrome were reported. It seems probable that the investigational approach to treat mental disorders by DBS will increase substantially. Neurosurgical interventions in psychiatric patients raise ethical considerations not only based on the disreputable experiences of the era of psychosurgery. Therefore, it is necessary to implement transparent and well-defined regulations for the protection of the patients as well as appropriate support for therapeutic research. The current article aims to provide a synopsis of the DBS approach in mental disorders and the hitherto existing criteria for research. It suggests some additional requirements for ethically justifiable therapeutic research employing DBS in psychiatric patients.
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This study aimed at investigating the neuropsychological effect of DBS of the Subthalamic Nucleus in patients with advanced Parkinson's disease (PD). A standardized neuropsychological test battery, assessing reasoning, memory and executive functions, was administered to 27 PD patients who underwent DBS-STN (DBS group) and to a matched control group of 31 PD patients under optimal medical treatment (MED group). Patients were evaluated at baseline and at the end of 1 year. Change score analysis (T1 minus T0 scores) demonstrated a significant decline in phonemic verbal fluency in the DBS group compared with the MED group (p < 0.005), while there were no significant changes between the two groups for the other cognitive tests. Single cases analysis by means of multivariate normative comparisons revealed that 4 out of 27 DBS patients (15%) showed cognitive deterioration one year post surgery. These patients were significantly more compromised from a motor standpoint (UPDRS, section III) than the 23 DBS PD patients who had no cognitive decline post surgery. Results of this prospective controlled-study showed that phonemic verbal fluency declined one year after DBS-STN, while the other cognitive domains did not change significantly. Nevertheless, single case analysis highlighted the fact that a subgroup comprising 15%