Deep brain stimulation is a well-established therapy for the motor symptoms of Parkinson’s disease, but there remains an opportunity to improve symptom relief. The temporal pattern of stimulation is a new parameter to consider in DBS therapy, and we compared the effectiveness of Temporally Optimized Patterned Stimulation to standard DBS at reducing the motor symptoms of PD. Twenty-six subjects with DBS for PD received three different patterns of stimulation while on medication and using stimulation parameters optimized for standard DBS. Side (...) effects and motor symptoms were assessed after 30 min of stimulation with each pattern. Subjects experienced similar types of side effects with TOPS and standard DBS, and TOPS were well-tolerated by a majority of the subjects. On average, the most effective TOPS was as effective as standard DBS at reducing the motor symptoms of PD. In some subjects a TOPS pattern was the most effective pattern. Finally, the TOPS pattern with low average frequency was found to be as effective or more effective in about half the subjects while substantially reducing estimated stimulation energy use. TOPS DBS may provide a new programing option to improve DBS therapy for PD by improving symptom reduction and/or increasing energy efficiency. Optimizing stimulation parameters specifically for TOPS DBS may demonstrate further clinical benefit of TOPS DBS in treating the motor symptoms of Parkinson’s disease. (shrink)

IntroductionDeep brain stimulation has become a standard treatment option for select patients with Parkinson’s disease. The selection process and surgical procedures employed have, to date, not been standardized.MethodsA comprehensive 58-question web-based survey was developed with a focus on DBS referral practices and peri-operative management. The survey was distributed to the Parkinson’s Foundation Centers of Excellence, members of the International Parkinson’s Disease and Movement Disorders Society, and the Parkinson Study Group between December 2015 and May 2016.ResultsThere were 207 individual respondents drawn (...) from 59 countries and 6 continents, of whom 64% received formal training in DBS. Thirteen percent of centers reported that DBS could proceed despite a confidence level of < 50% for PD diagnosis. A case-based approach to DBS candidacy was applied in 51.3% of centers without a cut-off for levodopa-responsiveness. Surprisingly, 33% of centers regularly used imaging for diagnostic confirmation of idiopathic PD. Thirty-one percent of centers reported that neuropsychological evaluation did not affect DBS target selection. Approximately half of the respondents reported determination of DBS candidacy based on a multidisciplinary committee evaluation and 1/3rd reported that a committee was used for target selection. Eight percent of respondents felt that psychosocial factors should not impact DBS candidacy nor site selection. Involvement of allied health professionals in the preoperative process was sparse. There was high variability in preoperative education about DBS outcome expectations. Approximately half of the respondents did not utilize a “default brain target,” though STN was used more commonly than GPi. Specific DBS procedure techniques applied, as well as follow-up timelines, were highly variable.ConclusionResults revealed high variability on the best approaches for DBS candidate selection, brain target selection, procedure type, and postoperative practices. Cognitive and mood assessments were underutilized. There was low reliance on multidisciplinary teams or psychosocial factors to impact the decision-making process. There were small but significant differences in practice across global regions, especially regarding multidisciplinary teams. The wide variability of responses across multiple facets of DBS care highlights the need for prospective studies to inform evidence-based guidelines. (shrink)

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

Background: Freezing of gait is a common symptom in Parkinson’s disease and can be difficult to treat with dopaminergic medications or with deep brain stimulation. Novel stimulation paradigms have been proposed to address suboptimal responses to conventional DBS programming methods. Burst-cycling deep brain stimulation delivers current in various frequencies of bursts, while maintaining an intra-burst frequency identical to conventional DBS.Objective: To evaluate the safety and tolerability of BCDBS in PD patients with FOG.Methods: Ten PD subjects with STN or GPi DBS (...) and complaints of FOG were recruited for this single center, single blinded within-subject crossover study. For each subject, we compared 4, 10, and 15 Hz BCDBS to conventional DBS during the PD medication-OFF state.Results: There were no serious adverse events with BCDBS. It was feasible and straightforward to program BCDBS in the clinic setting. The benefit was comparable to conventional DBS in measures of FOG, functional mobility and in PD motor symptoms. BCDBS had lower battery consumption when compared to conventional DBS.Conclusions: BCDBS was feasible, safe and well tolerated and it has potential to be a viable future DBS programming strategy. (shrink)

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

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

DBS Think Tank IX was held on August 25–27, 2021 in Orlando FL with US based participants largely in person and overseas participants joining by video conferencing technology. The DBS Think Tank was founded in 2012 and provides an open platform where clinicians, engineers and researchers can freely discuss current and emerging deep brain stimulation technologies as well as the logistical and ethical issues facing the field. The consensus among the DBS Think Tank IX speakers was that DBS expanded in (...) its scope and has been applied to multiple brain disorders in an effort to modulate neural circuitry. After collectively sharing our experiences, it was estimated that globally more than 230,000 DBS devices have been implanted for neurological and neuropsychiatric disorders. As such, this year’s meeting was focused on advances in the following areas: neuromodulation in Europe, Asia and Australia; cutting-edge technologies, neuroethics, interventional psychiatry, adaptive DBS, neuromodulation for pain, network neuromodulation for epilepsy and neuromodulation for traumatic brain injury. (shrink)

Substantial discussion in the neuroethical literature has addressed the possibility that deep brain stimulation (DBS) and adaptive DBS (aDBS) could result in changes in personality, agency, and ide...

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

John Martin Fischer's The Metaphysics of Free Will is devoted to two major projects. First, Fischer defends the thesis that determinism is incompatible with a person's control over alternatives to the actual future. Second, Fischer defends the striking thesis that such control is not necessary for moral responsibility. This review essay examines Fischer's arguments for each thesis. Fischer's defense of the incompatibilist thesis is the most innovative to date, and I argue that his formulation restructures the free will debate. To (...) defend his second thesis Fischer relies upon examples designed to show that an agent is responsible for an unavoidable action. I criticize Fischer's account of these examples, but I also maintain that my criticisms do not compromise his theory of responsibility. I raise several other difficulties for Fischer's theory of responsibility, and I close by offering some suggestions about how he might further defend it. (shrink)

The rapid advancement of technology has led to an explosion of speculative theories about what the future of humankind may look like. These "technological futurisms" have arisen from significant advances in the fields of nanotechnology, biotechnology and information technology and are drawing growing scrutiny from the philosophical and theological communities. This text seeks to contextualize the growing literature on the cultural, philosophical and religious implications of technological growth by considering technological futurisms such as transhumanism in the context of the long (...) historical tradition of technological dreaming. Michael Burdett traces the latent religious sources of our contemporary technological imagination by looking at visionary approaches to technology and the future in seminal technological utopias and science fiction and draws on past theological responses to the technological future with Pierre Teilhard de Chardin and Jacques Ellul. Burdett's argument arrives at a contemporary Christian response to transhumanism based around the themes of possibility and promise by turning to the works of Richard Kearney, Eberhard Jüngel and Jürgen Moltmann. Throughout, the author highlights points of correspondence and divergence between technological futurisms and the Judeo-Christian understanding of the future. (shrink)

Contemporary psycholinguistic models place significant emphasis on the cognitive processes involved in the acquisition, recognition, and production of language but neglect many issues related to the representation of language-related information in the mental lexicon. In contrast, a central tenet of network science is that the structure of a network influences the processes that operate in that system, making process and representation inextricably connected. Here, we consider how the structure found across phonological networks of several languages from different language families may (...) influence language processing as we age and experience diseases that affect cognition during the typical and atypical acquisition of new words, during typical perception and production of speech in adults, and during language change over time. We conclude that the network science approach may not only provide insights into specific language processes but also provide a way to connect the work from these domains, which are becoming increasingly balkanized. (shrink)

ABSTRACTThis article defends the importance of epistemic safety for legal evidence. Drawing on discussions of sensitivity and safety in epistemology, the article explores how similar considerations apply to legal proof. In the legal context, sensitivity concerns whether a factual finding would be made if it were false, and safety concerns how easily a factual finding could be false. The article critiques recent claims about the importance of sensitivity for the law of evidence. In particular, this critique argues that sensitivity does (...) not have much of an effect on the value of legal evidence and that it fails to explain legal doctrine. By contrast, safety affects the quality of legal evidence, and safety better explains central features of the law of evidence, including probative value, admissibility rules, and standards of proof. (shrink)

This essay concerns Scott Shapiro's criticism that H.L.A. Hart's theory of law suffers from a Although other philosophers of law have summarily dismissed Shapiro's criticism, I argue that it identifies an important requirement for an adequate theory of law. Such a theory must explain why legal officials justify their actions by reference to abstract propositional entities, instead of pointing to the existence of social practices. A virtue of Shapiro's planning theory of law is that it can explain this phenomenon. Despite (...) these sympathies, however, I end with the suggestion that Shapiro's criticism of Hart, as it stands, is incomplete. Careful attention to Hart's notion of the internal point of view indicates that he was aware that legal justification ends with abstract objects, not practices, and that he offered his own explanation of this phenomenon. (shrink)

The majority of the chapters in this edition of The Cognitive Neurosciences are new, and those from the first edition have been completely rewritten and updated ...

Ayn Rand's first novel, We the Living, offers an early form of the author's nascent philosophy—the philosophy Rand later called Objectivism. Robert Mayhew's collection of entirely new essays brings together pre-eminent scholars of Rand's writing. In part a history of We the Living, from its earliest drafts to the Italian film later based upon it, Mayhew's collection goes on to explore the enduring significance of Rand's first novel as a work both of philosophy and of literature.

This article explores the relationships between legal proof and fundamental epistemic concepts such as knowledge and justification. A survey of the legal literature reveals a confusing array of seemingly inconsistent proposals and presuppositions regarding these relationships. This article makes two contributions. First, it reconciles a number of apparent inconsistencies and tensions in accounts of the epistemology of legal proof. Second, it argues that there is a deeper connection between knowledge and legal proof than is typically argued for or presupposed in (...) the legal literature. This connection is illustrated through a discussion of the Gettier problem in epistemology. It is argued that the gap or disconnect between truth and justification that undermines knowledge in Gettier cases also potentially undermines the success of legal verdicts. (shrink)

Philosophical Issues, Volume 31, Issue 1, Page 280-298, October 2021.

In contrast to The Methods of Ethics, Sidgwick’s Practical Ethics counsels not trying to “get to the bottom of things” in our efforts to reach “some results of value for practical guidance and life.” For Sidgwick, both practical and theoretical ethics should start from the Morality of Common Sense. Although he retained his utilitarian outlook in Practical Ethics, this paper suggests that the Morality of Common Sense has the resources to hold its own against utilitarian revision.

In The Birth of the Clinic, The Order of Things, and Discipline and Punish, Foucault writes a "history of the present" by showing the connections between the archaeology of knowledge and criticism. In the first, he is fundamentally concerned with the changes in human perception evident at the end of the eighteenth century and the relation of these changes to the fundamental structures of experience. Underlying the history of medicine is the moral and political attempt to link the development of (...) science with the development of bourgeois freedom. In The Order of Things, he cites archaeology as a method of uncovering the fundamental paradigms of cultures and their systems of thought. Finally, in Discipline and Punish, he considers discourse a domain of power relations and thus establishes a link between knowledge and power. A "history of the present" is a self-conscious field of power relations and political struggle. (shrink)

Abstract Agent-based virtue ethics is a unitary normative theory according to which the moral status of actions is entirely dependent upon the moral status of an agent's motives and character traits. One of the problems any such approach faces is to capture the common-sense distinction between an agent's doing the right thing, and her doing it for the right (or wrong) reason. In this paper I argue that agent-based virtue ethics ultimately fails to capture this kind of fine-grained distinction, and (...) to this extent ought to be rejected. I focus first on Michael Slote's agent-based theory, according to which the moral status of actions depends upon an agent's actual motives, and argue that this leads to a paradox. I then consider whether the ?counterfactual? version of agent-basing favoured by Rosalind Hursthouse and Linda Zagzebski fares any better, and conclude that it does not. (shrink)

In this article I investigate the extent to which Bhikhu Parekh believes that a person's cultural/religious background must be preserved and whether, by implication, religious schooling is justified by his theory. My discussion will explore—by inference and implication—whether Parekh's carefully crafted multiculturalism, enriched and illuminated by numerous practical insights, is socially tenable. I will also consider whether, by extension, it is justifiable, on his line of reasoning, to cultivate cultural and religious understandings among one's own children. Finally, I will contend (...) that Parekh, notwithstanding his cautious, even‐handed approach, commits several important errors, including conflating the culture of the parents with that of the children and insisting that cultural and religious persons ought to be allowed to defend their views in the public square on religious grounds. (shrink)

Critical readings of the novels and essays by the Pakistani writer Mohsin Hamid tend to emphasize the social and political aspects of his work. In his discussion of Hamid's best known novel, Peter Morey, for example, affirms that "in both its form … and its content, The Reluctant Fundamentalist addresses contemporary questions about national vs globalized structures of power."1 He then goes on to cite Matthew Hart and Jim Hansen, for whom the novel "is concerned with subjects like cross-cultural romance, (...) transnational capitalism, and the limits of cosmopolitan space."2 As they see it, the story of Changez, the novel's protagonist, "is about the resurgence of inter-national politics from within the carapace of... (shrink)

In this reply, I seek to summarize fairly the criticisms advanced by each of my four critics, Jonathan Schaffer, Gideon Yaffe, John Gardner, and Carolina Sartorio. That there is so little overlap either in the aspects of the book on which they focus or in the arguments they advance about those issues has forced me to reply to each of them separately. Schaffer focuses much of his criticisms on my view that absences cannot serve as causal relata and argues that (...) this commits me to the view that double preventions cannot be causal of events such as deaths. I deny that double preventions such as beheadings are not causal, while admitting that other double preventions are not causal but denying that this latter conclusion is unwelcome in its implications. Yaffe criticizes my view that a person substantially causing some harm H is sufficient for that person having performed the activity of H-ing, whereas I affirm that causing H is sufficient for doing the action of H-ing even if it is not sufficient for intentionally H-ing. Gardner takes issue with my “experiential argument” for the relevance of causation to moral blame; he urges that we cannot infer that we are more guilty from either the psychological fact that we feel more guilty or from the moral fact that it is virtuous to feel such heightened guilt, because it is viciously circular: we feel such guilt only because we have already judged that we are more guilty, and it is virtuous to feel such guilt only because we in fact are more guilty. I deny such circularity exists. Sartorio takes issue with my thesis that in omissive overdetermination cases neither omitter is morally responsible for the harm. I trade intuitions with Sartorio about a range of related cases that we each think bears on the issue. (shrink)

My own mode of discussing Douglas Husak's excellent new book, Overcriminalization,1 is by comparing the theory that book defends—what Husak calls “minimalism”—with a theory with which I am already...