Am Berg--der erhabene Blick : Nietzsches Zarathustra, Flauberts Antonius -- Bergauf und bergab, immerzu : Nietzsches Zarathustra -- Zum Berg hin, immerdar : Flauberts Antonius -- Der ekstatische Blick : am Berg und bergab.

Sixteen years ago, Michael Ashburner and his colleagues proposed a hierarchical model for the genetic control of polytene chromosome puffing by the steroid hormone ecdysone. The recent molecular isolation and characterization of three early ecdysone‐inducible genes has confirmed many aspects of this model — these genes are directly induced by ecdysone, repressed by ecdysone‐induced proteins, and appear to encode DNA binding regulatory proteins. The three early genes are also remarkably similar in structure. They are all unusually long and complex, with (...) multiple transcripts that direct the synthesis of several related proteins from each locus. Proteins encoded by two of the early genes bind to both early and late ecdysone‐induced puffs, implying that they are key regulators in the hierarchy. (shrink)

Deep-brain stimulation has been used to treat advanced Parkinson disease and other neurological and psychiatric disorders that have not responded to other treatments. While deep-brain stimulation can modulate overactive or underactive regions of the brain and thereby improve motor function, it can also cause changes in a patient’s thought and personality. This paper discusses the trade-offs between the physiological benefit of this technique and the potential psychological harm.

Davis called for “extreme caution” in the use of non-invasive brain stimulation to treat neurological disorders in children, due to gaps in scientific knowledge. We are sympathetic to his position. However, we must also address the ethical implications of applying this technology to minors. Compensatory trade-offs associated with NIBS present a challenge to its use in children, insofar as these trade-offs have the effect of limiting the child’s future options. The distinction between treatment and enhancement has some normative force (...) here. As the intervention moves away from being a treatment toward being an enhancement—and thus toward a more uncertain weighing of the benefits, risks, and costs—considerations of the child’s best interests diminish, and the need to protect the child’s autonomy looms larger. NIBS for enhancement involving trade-offs should therefore be delayed, if possible, until the child reaches a state of maturity and can make an informed, personal decision. NIBS for treatment, by contrast, is permissible insofar as it can be shown to be at least as safe and effective as currently approved treatments, which are themselves justified on a best interests standard. (shrink)

Libet discovered that a substantial duration (> 0.5-1.0 s) of direct electrical stimulation of the surface of the somatosensory cortex at threshold currents is required before human subjects can report that a conscious somatosensory experience had occurred. Using a reaction time method we confirm that a similarly long stimulation duration at threshold currents is required for activation of elementary visual experiences (phosphenes) in human subjects following stimulation of the surface of the striate cortex. However, the reaction times (...) for the subject to respond to the cessation of the visual experience after the end of electrical stimulation could be as brief as 225-242 ms. We also carried out extensive studies in cats under a variety of anesthetic conditions using the same electrodes and parameters of stimulation employed in the human studies to study the patterns of neuronal activity beneath the stimulating surface electrode. Whereas sufficiently strong currents can activate neurons within milliseconds, stimulating currents close to threshold activate sustained neural activity only after at least 350-500 ms. When currents are close to threshold, some neurons are inhibited for several hundreds of millisecond before the balance between inhibition and excitation shifts towards excitation. These results suggest that the prolonged latencies, i.e., latencies beyond 200-250 ms, for the emergence of conscious experience following direct cortical stimulation result from a delay in the sustained activation of underlying cortical neurons at threshold currents rather than being due to any unusually long duration in central processing time. Intracellular records from cortical neurological cells during repetitive electrical stimulation of the surface of the feline striate cortex demonstrate that such stimulation induces a profound depolarizing shift in membrane potential that may persist after each stimulus train. Such a depolarization is evidence that extracellular K+ concentrations have increased during electrical stimulation. Such an increase in extracellular K+ progressively increases cortical excitability until the threshold for sustained activation of cortical neurons is reached and then exceeded. Consequently, the long latency for threshold activation of cortical neurons depends upon a dynamically increasing cortical facilatory process that begins hundreds of milliseconds before there is sustained activation of such neurons. In some cases, this facilatory process must overcome an initial stimulus-induced inhibition before neuronal firing commences. (shrink)

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. (shrink)

Auditory stimulation training (AST) has been proposed as a potential treatment for chil-dren with specific language impairments (SLI). The current study was designed to test this as-sumption by using an AST with technically modulated musical material (ASTM) in a random-ized control group design. A total of 101 preschool children (62 male, 39 females; mean age = 4.52 years, SD = 0.62) with deficits in speech comprehension and poor working memory ca-pacity were randomly allocated into one of two treatment groups (...) or a control group. Children in the ASTM group (n = 40) received three 30-minute sessions per week over 12 weeks, whereas children in the comparison group received pedagogical activities during these intervals (n = 24). Children in the control group (n = 37) received no treatment. Working memory, phoneme dis-crimination and speech perception skills were tested prior to (baseline) and after treatment. Chil-dren in the ASTM group showed significantly greater working memory capacity, speech per-ception, and phoneme discrimination skills after treatment, whereas children in the other groups did not show such improvement. Taken together, these results suggest that ASTM can enhance auditory cognitive performance in children with SLI. (shrink)

Multidisciplinary healthcare committees meet regularly to discuss patients’ candidacy for emerging functional neurosurgical procedures, such as Deep Brain Stimulation . Through debate and discussion around the surgical candidacy of particular patients, functional neurosurgery programs begin to mold practice and policy supported both by scientific evidence and clear value choices. These neurosurgical decisions have special considerations not found in non-neurologic committees. The professional time used to resolve these conflicts provides opportunities for the emergence of careful, ethical practices simultaneous with the (...) expansion of therapy applications. (shrink)

Deep Brain Stimulation (DBS) is a relatively new, experimental treatment for patients suffering from treatment-refractory Obsessive Compulsive Disorder (OCD). The effects of treatment are typically assessed with psychopathological scales that measure the amount of symptoms. However, clinical experience indicates that the effects of DBS are not limited to symptoms only: patients for instance report changes in perception, feeling stronger and more confident, and doing things unreflectively. Our aim is to get a better overview of the whole variety of changes (...) that OCD patients experience during DBS treatment. For that purpose we conducted in-depth, semi-structured interviews with 18 OCD patients. In this paper, we present the results from this qualitative study.We list the changes grouped in four domains: with regard to (a) person, (b) (social) world, (c)characteristics of person-world interactions, and (d) existential stance. We subsequently provide an interpretation of these results. In particular, we suggest that many of these changes can be seen as different expressions of the same process; namely that the experience of anxiety and tension gives way to an increased basic trust and increased reliance on one’s abilities. We then discuss the clinical implications of our findings, especially with regard to properly informing patients of what they can expect from treatment, the usefulness of including CBT in treatment, and the limitations of current measures of treatment success. We end by making several concrete suggestions for further research. (shrink)

Libet demonstrated that a substantial duration (>0.5-1.0 s) of direct electrical stimulation of the surface of a sensory cortex at a threshold or liminal current is required before a subject can experience a percept. Libet and his co-workers originally proposed that the result could be due either to spatial and temporal facilitation of the underlying neurons or additionally to a prolonged central processing time. However, over the next four decades, Libet chose to attribute the prolonged latency for evoking conscious (...) experience to a prolonged central processing time. In my view, Libet has not provided any convincing evidence, either on the basis of his own past work or in his critique of my paper, for his hypothesis of a central processing time exceeding 0.5s before conscious experience emerges following direct electrical threshold stimulation of the cortical surface. I stand by my original results and conclusion that such prolonged latencies are largely the consequence of a dynamically increasing cortical facilitatory process that begins hundreds of milliseconds before there is a sustained neuronal activation. In some cases, the facilitatory process must overcome an initial stimulus-induced inhibition before neuronal firing commences. (shrink)

We whole-heartedly agree with Mecacci and Haselager(2014) on the need to investigate the psychosocial effects of deep brain stimulation (DBS), and particularly to find out how to prevent adverse psychosocial effects. We also agree with the authors on the value of an embodied, embedded, enactive approach (EEC) to the self and the mind–brain problem. However, we do not think this value primarily lies in dissolving a so-called “maladaptation” of patients to their DBS device. In this comment, we challenge three (...) central claims of the authors on the basis of our direct experience with psychosocial effects of DBS in 45 obsessive- compulsive disorder (OCD) patients treated at the AMC in Amsterdam, The Netherlands, and our indepth qualitative interviews with 18 of them (de Haan et al. 2013). We end our comment by sketching out our perspective on the practical merits of an EEC approach to DBS. (shrink)

Puffing of polytene chromosomes is associated with intense genetic activity. Genetic determinants of puffing in Drosophila can now be dissected by transplanting genes known to puff to other chromosomal locations by transposonmediated germ line transformation. Recent studies show that induction of a heat shock puff requires only about one hundred and fifty base pairs of DNA upstream of the gene, around the start of transcription, and not the protein coding sequence itself. Moreover, the size of the ‘ectopic’ (...) class='Hi'>puff was found to be related to the size of the corresponding transcript. Similar work is now in progress with hormonally‐controlled puffs. (shrink)

The goal of this article is to shed light on Deep Brain Stimulation (DBS) postoperative suicidality risk factors within Treatment Resistant Depression (TRD) patients, in particular by focusing on the ethical concern of enrolling patient with history of self-estrangement, suicide attempts and impulsive–aggressive inclinations. In order to illustrate these ethical issues we report and review a clinical case associated with postoperative feelings of self-estrangement, self-harm behaviours and suicide attempt leading to the removal of DBS devices. Could prospectively identifying and (...) excluding patients with suicidality risk factors from DBS experimental trials—such as history of self-estrangement, suicide attempts and impulsive–aggressive inclinations—lead to minimizing the risk of suicidality harm? (shrink)

One of the topics that often comes up in ethical discussions of deep brain stimulation (DBS) is the question of what impact DBS has, or might have, on the patient’s self. This is often understood as a question of whether DBS poses a “threat” to personal identity, which is typically understood as having to do with psychological and/or narrative continuity over time. In this article, we argue that the discussion of whether DBS is a “threat” to continuity over time (...) is too narrow. There are other questions concerning DBS and the self that are overlooked in discussions exclusively focusing on psychological and/or narrative continuity. For example, it is also important to investigate whether DBS might sometimes have a positive (e.g. a rehabilitating) effect on the patient’s self. To widen the discussion of DBS, so as to make it encompass a broader range of considerations that bear on DBS’s impact on the self, we identify six features of the commonly used concept of a person’s “true self”. We apply these six features to the relation between DBS and the self. And we end with a brief discussion of the role DBS might play in treating otherwise treatment-refractory anorexia nervosa. This further highlights the importance of discussing both continuity over time and the notion of the true self. (shrink)

Although being generally safe, the use of Deep Brain Stimulation has been associated with a significant number of patients experiencing postoperative psychological and neurological harm within experimental trials. A proportion of these postoperative severe adverse effects have lead to the decision to medically prescribe device deactivation or removal. However, there is little debate in the literature as to what is in the patient’s best interest when device removal has been prescribed; in particular, what should be the conceptual approach to (...) ethically guide the decision to remove or maintain implants. The purpose of this article is to examine the ethical issues raised when patients refuse brain device explantation despite medical prescription. In order to illustrate these issues, we report and discuss a clinical case involving a patient suffering from treatment resistant depression who experienced forms of postoperative self-estrangement, as well as suicidal attempts, but who resists giving consent to device explantation. (shrink)

Ethical evaluation of deep brain stimulation as a treatment for Parkinson’s disease is complicated by results that can be described as involving changes in the patient’s identity. The risk of becoming another person following surgery is alarming for patients, caregivers and clinicians alike. It is one of the most urgent conceptual and ethical problems facing deep brain stimulation in Parkinson’s disease at this time. In our paper we take issue with this problem on two accounts. First, we elucidate (...) what is meant by “becoming another person” from a conceptual point of view. After critically discussing two broad approaches we concentrate on the notion of “individual identity” which centers on the idea of “core attitudes”. Subsequently we discuss several approaches to determine what distinguishes core attitudes from those that are more peripheral. We argue for a “foundational-function model” highlighting the importance of specific dependency relations between these attitudes. Our second aim is to comment on the possibility to empirically measure changes in individual identity and argue that many of the instruments now commonly used in selecting and monitoring DBS-patients are inappropriate for this purpose. Future research in this area is advised combining a conceptual and an empirical approach as a basis of sound ethical appraisal. (shrink)

Many studies have discussed the neural basis of asset bubbles. They found that the dorsolateral prefrontal cortex (DLPFC) played an important role in bubble formation, but whether a causal relationship exists and the mechanism of the effect of the DLPFC on bubbles remains unsettled. Using transcranial direct current stimulation (tDCS), we modulated the activity of the DLPFC and investigated the causal relationship between the DLPFC and the asset bubble in the classical learning-to-forecast experiment. 126 subjects were randomly divided into (...) three groups and received different stimulations (left anodal/right cathodal, right anodal/left cathodal or sham stimulation) respectively. We also conducted a 2-back task before and after stimulation to measure changes in subjects’ cognitive abilities and explore in detail the cognitive mechanism of the effect of DLPFC stimulation on asset bubbles. Based on our results, we found that the bubble of the left anodal/right cathodal stimulation group was significantly smaller than that of the sham stimulation group. In the meantime, subjects performed significantly better in the 2-back task after left anodal/right cathodal stimulation but not right anodal/left cathodal or sham stimulation, which is consistent with their performance in the learning-to-forecast experiment, supporting the cognitive mechanism to some extent. Furthermore, we examined different forecasting rules across individuals and discovered that the left anodal/right cathodal stimulation group preferred the adaptive learning rule, while the sham and right anodal/left cathodal stimulation groups adopted a pure trend-following rule that tended to intensify market volatility aggressively. (shrink)

A growing literature has recognized the importance of mental simulation (e.g., imagining alternatives to reality) in sparking creativity. In this chapter, we examine how counterfactual thinking, or imagining alternatives to past outcomes, affects group creativity. We explore these effects by articulating a model that considers the influence of counterfactual thinking on both the cognitive and social processes known to impact group creative performance. With this framework, we aim to stimulate research on group creativity from a counterfactual perspective.

Patient narratives from two investigational deep brain stimulation trials for traumatic brain injury and obsessive‐compulsive disorder reveal that injury and illness rob individuals of personal identity and that neuromodulation can restore it. The early success of these interventions makes a compelling case for continued post‐trial access to these technologies. Given the centrality of personal identity to respect for persons, a failure to provide continued access can be understood to represent a metaphorical identity theft. Such a loss recapitulates the pain (...) of an individual's initial injury or illness and becomes especially tragic because it could be prevented by robust policy. A failure to fulfill this normative obligation constitutes a breach of disability law, which would view post‐trial access as a means to achieve social reintegration through this neurotechnological accommodation. (shrink)

RESUMEN En el presente artículo se reconoce la significación de la estimulación prenatal de la comunicación y la necesidad de brindar una orientación familiar oportuna y certera tanto a la embarazada como a sus familiares y su objetivo está encaminadoa contribuir a la capacitación del personal de salud dirigida a la orientación a la familia para la estimulación prenatal de la comunicación. En él se tiene en cuenta la influencia de los médicos y enfermeras, en dicha labor, además, se encuentran (...) reflexiones, comentarios, acciones y técnicas, con el propósito de elevar la calidad de la orientación para que la familia potencie la estimulación de la comunicación desde la gestación. ABSTRACT In this paper, it is recognized the significance of prenatal communication stimulation and the need to give timely and appropriate family guidance to pregnant women and their families in order to contribute to health staff training towards family guidance on prenatal communication stimulation. It is taken into account the influence of doctors and nurses on this work. Thoughts, comments, actions and techniques can be found in order to improve guidance quality so that families encourage communication stimulation from gestation. (shrink)

Stimulants have been shown to be safe and effective for reduction of the symptoms of attention deficit hyperactivity disorder. Despite much debate, however, there has been little empirical evidence as to whether stimulants affect authenticity and moral agency in children. Singh presents evidence that stimulants do not undercut children's' sense of self and increase their experience of agency. These findings are consistent with laboratory evidence that stimulant drugs in therapeutic doses improve cognitive control over thought and behavior.

Elevations in brain stimulation reward (BSR) thresholds have been observed in rats undergoing nicotine withdrawal and have been proposed as a sensitive measure of the negative affective state associated with nicotine withdrawal. mGluR are presynaptic autoreceptors that decrease glutamate release when stimulated. The aim of this study was to examine the role of glutamate neurotransmission in nicotine dependence. The mGluR agonist LY314582 (2.5–7.5 mg/kg) precipitated nicotine withdrawal as measured by elevations in BSR thresholds in nicotine-treated rats but not in (...) controls. It was hypothesized that LY314582 precipitated nicotine withdrawal by decreasing glutamatergic tone at postsynaptic glutamate receptors. Therefore, the effects of MPEP (0.5–2 mg/kg), an mGluR antagonist, and MK-801 (0.01–1 mg/kg), an NMDA receptor antagonist, were examined. MPEP elevated BSR thresholds by an equal magnitude in control and nicotine-treated rats. At low doses, MK-801 (0.01–0.2 mg/kg) lowered BSR thresholds to a similar extent in control and nicotine-treated rats. At higher doses, MK-801 (0.25–1 mg/kg) disrupted performance in nicotine-treated and control rats. These data indicate that mGluR and NMDA receptors regulate BSR in opposite directions in non-dependent animals, and chronic nicotine treatment does not alter these effects. Most importantly, the data demonstrate that the mGluR is involved in nicotine dependence, but mGluR and NMDA receptors do not mediate mGluR actions in nicotine dependence. (shrink)

In this paper, we engage in dialogue with Jonathan Pugh, Hannah Maslen, and Julian Savulescu about how to best interpret the potential impacts of deep brain stimulation on the self. We consider whether ordinary people’s convictions about the true self should be interpreted in essentialist or existentialist ways. Like Pugh et al., we argue that it is useful to understand the notion of the true self as having both essentialist and existentialist components. We also consider two ideas from existentialist (...) philosophy – Jean-Paul Sartre and Simone de Beauvoir’s ideas about “bad faith” and “ambiguity” – to argue that there can be value to patients in regarding themselves as having a certain amount of freedom to choose what aspects of themselves should be considered representative of their true selves. Lastly, we consider the case of an anorexia nervosa-patient who shifts between conflicting mind-sets. We argue that mind-sets in which it is easier for the patient and his or her family to share values can plausibly be considered to be more representative of the patient’s true self, if this promotes a well-functioning relationship between the patient and the family. However, we also argue that families are well-advised to give patients room to figure out what such shared values mean to them, since it can be alienating for patients if they feel that others try to impose values on them from the outside. (shrink)

It has been well documented that the auditory system in the superior temporal cortex is responsible for processing basic auditory sound features, such as sound frequency and intensity, while the prefrontal cortex is involved in higher-order auditory functions, such as language processing and auditory episodic memory. The temporal auditory cortex has vast forward anatomical projections to the prefrontal auditory cortex, connecting with the lateral, medial, and orbital parts of the prefrontal cortex. The connections between the auditory cortex and the prefrontal (...) cortex thus help in localizing, recognizing, and comprehending external auditory inputs. In addition, the medial prefrontal cortex is believed to be a core region of episodic memory retrieval and is one of the most important regions in the default mode network. However, previous neural evidence with regard to the comparison between basic auditory processing and auditory episodic memory retrieval mainly comes from fMRI studies. The specific neural networks and the corresponding critical frequency bands of neuronal oscillations underlying the two auditory functions remain unclear. In the present study, we reported results of direct cortical stimulations during stereo-electro-encephalography recording in a patient with drug-resistant epilepsy. Electrodes covered the superior temporal gyrus, the operculum and the insula cortex of bilateral hemispheres, the prefrontal cortex, the parietal lobe, the anterior and middle cingulate cortex, and the amygdala of the left hemisphere. Two types of auditory hallucinations were evoked with direct cortical stimulations, which were consistent with the habitual seizures. The noise hallucinations, i.e., “I could hear buzzing noises in my head,” were evoked with the stimulation of the superior temporal gyrus. The episodic memory hallucinations “I could hear a young woman who was dressed in a red skirt saying: What is the matter with you?,” were evoked with the stimulation of MPFC. The patient described how she had met this young woman when she was young and that the woman said the same sentence to her. Furthermore, by analyzing the high gamma power induced by direct electrical stimulation, two dissociable neural networks underlying the two types of auditory hallucinations were localized. Taken together, the present results confirm the hierarchical processing of auditory information by showing the different involvements of the primary auditory cortex vs. the prefrontal cortex in the two types of auditory hallucinations. (shrink)

Although philosophers have explored several connections between neuroscience and moral responsibility, the issue of how real-world neurological modifications, such as Deep Brain Stimulation, impact moral responsibility has received little attention. In this article, we draw on debates about the relevance of history and manipulation to moral responsibility to argue that certain kinds of neurological modification can diminish the responsibility of the agents so modified. We argue for a historicist position - a version of the history-sensitive reflection view - and (...) defend that account against a rival, relational view of responsibility. We conclude that DBS can, under certain conditions, diminish responsibility, and explore the circumstances under which this might be so. We conclude by suggesting that philosophical debates about moral responsibility, manipulation, and history have greater practical relevance than is sometimes thought, and that attention to practical cases can help inform and deepen this body of scholarship. (shrink)