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)

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)

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)

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)

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)

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)

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)

From the concrete experience of war, Michael S. Yandell constructs a phenomenology of “negative revelation” in which false or distorted claims of goodness and justice disintegrate and become meaningless, adding depth to the term moral injury.

The third edition of a work that defines the field of cognitive neuroscience, with extensive new material including new chapters and new contributors.

Whataboutism is een strategie waarbij op een beschuldiging wordt gereageerd met een wedervraag die eveneens een beschuldiging impliceert, waardoor de oorspronkelijke vraag eerder wordt ontweken dan beantwoord. Het is een effectieve methode om de aandacht te verplaatsen naar een andere situatie door een vergelijkbaar, dan wel onvergelijkbaar, contrast te bieden, waardoor de beschuldigde het eigen gedrag probeert te rechtvaardigen en verantwoordelijkheid probeert te ontlopen. Maar niet alle vormen van whataboutism impliceren echter een drogredenering, noch worden ze altijd verkeerd toegepast. Het (...) contrast dat voortkomt uit de vraag ‘what about’ kan dan een cruciale bijdrage leveren aan een situatie die een verdere kritische analyse vereist, en daarmee de geloofwaardigheid van de argumentatie versterken. (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)

A recalcitrant emotion is one which conflicts with evaluative judgement. (A standard example is where someone is afraid of flying despite believing that it poses little or no danger.) The phenomenon of emotional recalcitrance raises an important problem for theories of emotion, namely to explain the sense in which recalcitrant emotions involve rational conflict. In this paper I argue that existing ‘neojudgementalist’ accounts of emotions fail to provide plausible explanations of the irrationality of recalcitrant emotions, and develop and defend my (...) own neojudgementalist account. On my view, recalcitrant emotions are irrational insofar as they incline the subject to accept an evaluative construal that the subject has already rejected. (shrink)

Originally published: Oxford: Clarendon, 1997.

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)

The concept of causation is fundamental to ascribing moral and legal responsibility for events. Yet the precise relationship between causation and responsibility remains unclear. This book clarifies that relationship through an analysis of the best accounts of causation in metaphysics, and a critique of the confusion in legal doctrine.

Cover -- Half Title -- Title Page -- Copyright Page -- Table of Contents -- List of Contributors -- Preface -- Foreword -- Introduction -- Chapter 1 Alternate Possibilities and Moral Responsibility -- Chapter 2 Responsibility and Alternative Possibilities -- Chapter 3 Blameworthiness and Frankfurt's Argument Against the Principle of Alternative Possibilities -- Chapter 4 In Defense of the Principle of Alternative Possibilities: Why I Don't Find Frankfurt's Argument Convincing -- Chapter 5 Responsibility, Indeterminism and Frankfurt-style Cases: A Reply to (...) Mele and Robb -- Chapter 6 Classical Compatibilism: Not Dead Yet -- Chapter 7 Bbs, Magnets and Seesaws: The Metaphysics of Frankfurt-style Cases -- Chapter 8 Moral Responsibility without Alternative Possibilities -- Chapter 9 Freedom, Foreknowledge and Frankfurt -- Chapter 10 Source Incompatibilism and Alternative Possibilities -- Chapter 11 Robustness, Control, and the Demand for Morally Significant Alternatives: Frankfurt Examples with Oodles and Oodles of Alternatives -- Chapter 12 Alternate Possibilities and Reid's Theory of Agent-causation -- Chapter 13 Responsibility and Agent-causation -- Chapter 14 Soft Libertarianism and Flickers of Freedom -- Chapter 15 'Ought' Implies 'Can', Blameworthiness, and the Principle of Alternate Possibilities -- Chapter 16 The Moral Significance of Alternate Possibilities -- Chapter 17 The Selling of Joseph - A Frankfurtian Interpretation -- Chapter 18 Some Thoughts Concerning PAP -- Bibliography -- Index. (shrink)

The concept of causation is fundamental to ascribing moral and legal responsibility for events. Yet the precise relationship between causation and responsibility remains unclear. This book clarifies that relationship through an analysis of the best accounts of causation in metaphysics, and a critique of the confusion in legal doctrine. The result is a powerful argument in favour of reforming the moral and legal understanding of how and why we attribute responsibility to agents.

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)

In Consciousness and the Social Brain, Princeton neuroscientist Michael Graziano lays out an audacious new theory to account for the deepest mystery of them all.

The elephant in the room -- Crabs and octopuses -- The central intelligence of a frog -- The cerebral cortex and consciousness -- Social consciousness -- Yoda and Darth: how can we find -- Consciousness in the brain? -- The hard problem and other perspectives on consciousness -- Conscious machines -- Uploading minds -- How to build visual consciousness.

There is a loud and persistent drum beat of support for schools, for citizenship, for diversity and inclusion, and increasingly for labor market readiness with very little critical attention to the assumptions underlying these agendas, let alone to their many internal contradictions. Accordingly, in this book I examine the philosophical, motivational, and practical challenges of education theory, policy, and practice in the twenty-first century. As I proceed, I do not neglect the historical, comparative international context so essential to better understanding (...) where we are, as well as what is attainable in terms of educational justice. I argue that we must constructively critique some of our most cherished beliefs about education if we are to save the hope of real justice from the rhetoric of imagined justice. (shrink)

The article explores the agreements and disagreements between the author and the authors of Responsible Brains on how neuroscience relates to moral responsibility. The agreements are fundamental: neuroscience is not the harbinger of revolutionary revision of our views of when persons are morally responsible for the harms that they cause. The disagreements are in the details of what is needed for neuroscience to be the helper of the moral sciences.

This work provides, for the first time, a unified account of the theory of action presupposed by both British and American criminal law and its underlying morality. It defends the view that human actions are volitionally caused body movements. This theory illuminates three major problems in drafting and implementing criminal law--what the voluntary act requirement does and should require, what complex descriptions of actions prohibited by criminal codes both do and should require, and when the two actions are the "same" (...) for purposes of assessing whether multiple prosecutions and multiple punishments are warranted. The book contributes to the development of a coherent theory of action in philosophy. It provides a grounding in three of the most basic elements of criminal liability for legislators, judges, and the lawyers who argue to them. (shrink)

"The Cognitive Neurosciences III is a magnificent accomplishment. It covers topics trom ions to consciousness, from reflexes to social psychology. ...

Message from the planet -- When prophecy fails -- Energy and empire -- Climate economics -- Ethical emissions -- Dwelling in the light -- Mobility and pilgrimage -- Faithful feasting -- Remembering in time.

This book addresses the philosophical questions that arise when neuroscientific research and technology are applied in the legal system. The empirical, practical, ethical, and conceptual issues that Pardo and Patterson seek to redress will deeply influence how we negotiate and implement the fruits of neuroscience in law and policy in the future.

The experience of a reward appears to enhance memory for recent prior events, adaptively making that information more available to guide future decision-making. Here, we tested whether reward enhances memory for associative item-location information and also whether the effect of reward spreads to other categorically-related but unrewarded items. Participants earned either points (Experiment 1) or money (Experiment 2) through a time-estimation reward task, during which stimuli-location pairings around a 2D-ring were shown followed by either high-value or low-value rewards. All stimuli (...) were then tested for location memory or recognition (yes/no), immediately and after a 24-hour delay. Across both experiments (combined analysis), there was a robust improvement in location memory following high-value rewards, even though evidence supporting this effect was reliable in Experiment 2 but not in Experiment 1. The memory-enhancing effect of reward was observed on both the immediate and delayed location-memory tests. Reward-enhanced memory for both directly rewarded stimuli and categorically related stimuli that were not directly rewarded. No reliable effect of reward value on yes/no recognition-memory performance was observed in either experiment. We hypothesise that reward enhances the consolidation of recent experience and conceptually related memories to make these more available for future decisions. (shrink)

In various areas of Anglo-American law, legal liability turns on causation. In torts and contracts, we are each liable only for those harms we havecausedby the actions that breach our legal duties. Such doctrines explicitly make causation an element of liability. In criminal law, sometimes the causal element for liability is equally explicit, as when a statute makes punishable any act that has “caused… abuse to the child….” More often, the causal element in criminal liability is more implicit, as when (...) criminal statutes prohibitkillings, maimings, rapings, burnings, etc. Such causally complex action verbs are correctly applied only to defendants who have caused death, caused disfigurement, caused penetration, caused fire damage, etc. (shrink)