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: 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...

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)

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)

This commentary on Philip Kitcher’s book What’s the Use of Philosophy? addresses two questions. First, must philosophers be methodologically self-conscious to do good work? Second, is there value in the questions pursued in the traditional areas of analytic philosophy?

The aging of attentional and emotional functions has been extensively studied but relatively independently. Therefore, the relationships between aging and the interactions of attentional and emotional processes remain elusive. This study aimed to determine how age affected the interactions between attentional and emotional processes during adulthood. One-hundred forty adults aged 18–79 performed the emotional variant of the Attention Network Test, which probed alerting, orienting, and executive control in the presence and absence of threatening faces. During this task, contexts with varying (...) levels of task preparatory processes were created to modulate the effect of threatening faces on attention, and functional near-infrared spectroscopy (fNIRS) was used to examine the neural underpinnings of the behavioural effects. The behavioural results showed that aging was associated with a significant decline in alerting efficiency, and there was a statistical trend for age-related deficits in executive control. Despite these age differences, age did not significantly moderate the interactions among attentional networks or between attention and emotion. Additionally, the fNIRS results showed that decreased frontal cortex functioning might underlie the age-related decline in executive control. Therefore, while aging has varying effects on different attentional networks, the interactions of attentional and emotional processes remain relatively unaffected by age. (shrink)

Wedin addresses the debate over whether nonsubstantial individuals, that inhere in a subject but are not said of a subject, i.e. accidents, such as the pallor of Socrates, are nonrecurring particulars or a kind of determinate universal. Wedin examines the secondary literature on this topic and divides it into two schools of thought, determined by the contributions of J.L. Ackrill and G.E.L. Owen. According to Ackrill, individuals in non‐substance categories are particular to the substance they are in; Owen critiques Ackrill's (...) view, and proposes that these items can recur in more than one subject and hence are a sort of universal. Wedin finds Owen's thesis unsatisfactory, even after supplementing it with an improved version due to Michael Frede; instead, Wedin argues for a revised version of Ackrill's interpretation of nonsubstantial individuals as nonrecurrent particulars. According to Wedin, Aristotle is committed to individuals only—e.g. to Socrates and to the particular bit of pallor in him: this conclusion has an important bearing on the ontological status of individuals and on the primacy of substance to nonsubstantial items. (shrink)

Wedin considers the problem of the compatibility of the Categories account of primary substance with the theory of substantial form of the Metaphysics. Wedin collects from the secondary literature the most important arguments for incompatibilism, and offers some proposals for restoring their harmony. While admitting the evident differences in the way Aristotle treats the question of substance in each treatise, Wedin is keen to argue that these differences are not sufficient to conclude that the treatises are incompatible. Wedin singles out (...) for particular attention, and criticism, Michael Frede and Gunther Patzig's account of Metaphysics Zeta, according to which the primary substance of the Metaphysics and the basic subject of predications is the form. Wedin considers two ‘philosophical’ arguments and one ‘Aristotelian’ argument for the subjecthood of forms, and argues that the textual evidence does not support the claim that form is the subject of accidents. (shrink)

Michael J. Zimmerman explores whether and how our ignorance about ourselves and our circumstances affects what our moral obligations and moral rights are. He rejects objective and subjective views of the nature of moral obligation, and presents a new case for a 'prospective' view.

Wedin considers the relation between the ontological commitment in the Categories and the semantical theory of underlying ontological configurations for standard categorical statements. According to Wedin, Aristotle's fourfold division of beings, which divides things according to whether they are, or are not, said of, and/or present in a subject, is a meta‐ontology that is concerned with beings per se, i.e. the fundamental things that are. Wedin explains that the primacy of c‐substance involves an asymmetry in the relation between c‐substance and (...) everything else, or between the substantial and the nonsubstantial. This is because there is an ontological dependence of non‐substances, and also of secondary substances, on substances: everything is either said of, or in, primary substance. The argument of this chapter, then, is that the world of the Categories is a world of individuals: all ontological relations needed for semantics can be accommodated by appeal to individuals only. (shrink)

Wedin argues that Aristotle makes form the substance of c‐substances because it is the essence of the c‐substance. Much of this chapter consists of a careful examination of a passage in Metaphysics Zeta 4, which Wedin calls the ‘New Primacy Passage’, that is crucial to Wedin's overall thesis, because here Aristotle appeals to a notion of definitional primacy, as opposed to the ontological primacy of the Categories. Z.4 focuses on this claim that form must be essence: Wedin argues that essence (...) is a certain kind of form, a form of a genus ; this does not mean ‘species’, as some commentators have thought. This is because the species is a combination of form and matter, whereas the genous eidos, Wedin argues, is the formal part only of the definition that applies to the thing. On Wedin's account, Aristotle introduces the notion of explanatory primacy of form in Z.4. (shrink)

Wedin offers an interpretation of Metaphysics Zeta 13, a very important and difficult chapter, where Aristotle apparently denies that substance is a universal, having, on most accounts, already claimed that form is substance, and that form is a universal. This interpretation of the argument of Z.13, Wedin argues, threatens the possibility of attaining a definition of substance, and places in doubt what has gone before in the treatise. According to Wedin, what Aristotle is concerned with in Z.13 is not the (...) denial that substance is a universal but rather with the denial that anything predicated universally of a c‐substance is the substance‐of the c‐substance, which Wedin calls ‘Weak proscription’. In Wedin's account of Z.13, then, Aristotle is continuing to pursue issues first raised in Z.10–11 that have to do with the relations between form and definition, and form and the universal. Wedin also argues that the dilemma at the conclusion of Z.13, regarding the definability of substance, is resolved in Z.16, with the notion of ‘Dual Complexity’, according to which the parts of a form exist potentially in the form, just as the parts of the c‐substance exist potentially in the c‐substance. (shrink)

Chapters 10 and 11 are critical to the argument of Metaphysics Zeta: these chapters are concerned with the purification of form. Z.10 introduces the apparatus of part and whole and consists of an argument to the end that form and its parts have priority over the other internal structural components of c‐substances, i.e. matter and the compound of form and matter; while in Z.11 Aristotle argues that form and its parts cannot involve any admixture of matter. Wedin argues that the (...) causal role of form presupposes its purity: if form is to explain why a certain portion of matter constitutes a c‐substance of a given kind, then matter—whether this latter is understood as functional, or remnant matter—cannot already be contained in the form. This is the ‘purity thesis’, as Wedin calls it: matter cannot be included in the definitions of natural organisms, Wedin points out, because that would make the explanandum a part of the principle that explains it. Wedin also argues that form must be sufficiently complex to provide definitions of the natures of particular compounds, which are complex, even though form itself is a kind of universal. (shrink)

In the Metaphysics, Aristotle often says that ‘form is substance’: in this chapter, Wedin argues that ‘substance’ in this context means the ‘substance‐of’ c‐substances. Wedin begins by examining Aristotle's use, and retention, of the framework of the Categories in Metaphysics Zeta, before turning to discuss Z.3, which is crucial to understanding the relation between the Categories and Metaphysics theories of substance, because it is usually thought that here Aristotle departs from the substance of the Categories. Wedin denies that Z.3 involves (...) a rejection of the Categories subjecthood criterion for primary substance: Aristotle rejects only the claim that one thing is the substance of another simply if it is the primary underlying subject of the other. Wedin argues that in Z.3 Aristotle introduces the idea of the ‘substance‐of’ a thing, and identifies as candidates for the substance of c‐substances the internal structural components form, matter, and the compound of form and matter. (shrink)

Wedin discusses Aristotle's claims in Metaphysics Zeta 6 that the essence of a thing is to be sought among its per se attributes, and that each thing that is primary and spoken of per se, e.g. primary substance, is the same as its essence. Wedin argues that the Zeta 6 Thesis, i.e. that the essence of a thing is the thing's immediate essence, is a crucial requirement of the explanatory role of essence as the substance of c‐substances. According to Wedin, (...) Aristotle introduces this requirement in order to establish that a thing's essence cannot depend on another essence. Form must be the essence; if form cannot explain the nature of the thing of which it is the form, there would be the threat of a regress of explanatory forms. At the end of the chapter, Wedin considers the problem that the identity of a thing and its essence is a requirement that can be met by non‐substance items, but he denies that this leads to a dilution of the conception of substance. (shrink)

Aristotelian virtue ethics does not treat motives or even character as the grounding basis for the rest of ethics, but the present agent‐based approach does. However, there are objections to agent‐basing that need to be considered. Having answered those objections, the chapter discusses three major forms of agent‐based virtue ethics: a somewhat less than plausible ”morality as inner strength” ; ”morality as universal benevolence” ; and ”morality as caring”. Any agent‐based morality does well to treat overall motivation, rather than occasional (...) single motives, as the fundamental basis for ethical characterizations. (shrink)

A commonsense virtue ethics can contribute to moral education by pointing out the importance of self‐regarding virtues. That importance is often ignored or neglected in school ”values” curricula.

Even though commonsense virtue ethics is less unified than utilitarianism, various forms of pluralism are inherent in utilitarianism.

Kantian and commonsense moral thinking are incoherent because self‐other asymmetry does not cogently combine with the belief that we owe more to people the closer they are to us in familial or personal terms. The latter is commonsensically explained by the claim that it is natural or inevitable that we should care about those closer to us more than about those less close to us, but this seemingly plausible assumption tends to undercut the justification that is typically and intuitively offered (...) for self‐other asymmetry, namely, that we naturally care more about ourselves than about others, so that there is no need to assume any duty to avoid harming oneself. A commonsense ethics of virtue avoids this and other incoherences or tensions in Kantian and commonsense moral thinking. (shrink)

Commonsense views about practical rationality are self‐other asymmetric in a way diametrically opposed to the asymmetry involved in commonsense or Kantian morality. What is likely to harm others does not count as irrational in the same fundamental way that what is likely to harm oneself does. Commonsense or Kantian morality is agent sacrificingly asymmetrical, whereas commonsense rationality is agent favouringly asymmetrical. This means that these two parts of ordinary thinking tug in opposite directions, but a virtue‐ethical approach that focuses exclusively (...) on commonsense thinking about what is admirable or counts as a virtue lacks this sort of tension, and such greater unity counts in its favor. (shrink)

Is an agent‐based sentimentalist virtue ethics of caring or benevolence sufficiently action‐guiding, given the focus on the inner life rather than external factors? The answer is that such forms of ethics are not meant to be practical in this sense, because a focus on what is right or obligatory takes the agent away from a praiseworthy focus on the good of other individuals. The ideal agent is deeply connected with and directly concerned about the welfare of others, and such a (...) person does not conscientiously worry about whether he or she is acting rightly or virtuously. This conclusion allows us to understand moral growth and moral conflict – though in a way different from the way in which the Kantian tradition, with its emphasis on conscientiousness, does. (shrink)

Virtue ethics treats aretaic, as opposed to deontic, concepts as fundamental and focuses in the first instance on character traits or motives rather than actions. Virtue ethics also contrasts with utilitarianism because although both these approaches are self‐other symmetric, they embrace different forms of symmetry. Utilitarianism holds that one's concern for oneself should be no different, fundamentally, from the concern one has for each and every other individual. But such ”in sensu diviso” symmetry differs from an ”in sensu composito” symmetry (...) that would have us be equally concerned with ourselves and with others considered as a class. Commonsense virtue ethics subscribes to the latter kind of symmetry because of the way in which it gives equal or nearly equal weight to both self‐benefiting and other‐benefiting virtues. (shrink)

Looks at akrasia, monism, and pluralism. Many deem akrasia conceptually incoherent. Others, notably David Wiggins, argue that coherence is secured in so far as incommensurable values are present. Against these views, it is argued that coherent akrasia is possible, and that it requires the distinction between the cognitive and the affective, and not between comparable and commensurable values. Akrasia extends to monistic theories––a monistic theory, e.g. hedonism, is compatible with akrasia. Akratic conflict does not require plurality. An account of reasons, (...) which goes beyond value finality and value maximization, emerges. (shrink)

Philosophers commonly argue that conflicts of values are deeply problematic for ethical theories in so far as they force the theories into impracticality, incompleteness, or irrealism. To be complete, a theory must tell us in every case what must be done. To be practical, it must never tell us to do what is impossible. As conflict seems to involve just these features, some philosophers argue from the fact that avoiding conflict is impossible to the conclusion that ethical theories must either (...) be silent in some cases or that it requires us to do both of the jointly impossible acts. Others seek to explain the conflict away as merely apparent. Against these views, it is argued that mere incompossibility does not make for a conflict. All choice involves incompossibility, but not all choice involves conflict. Conflict must be understood in terms of what is conflicting. Understanding this requires seeing that many act evaluations are not action‐guiding. (shrink)

Examines arguments that maximization holds for conceptual reasons. Looks at maximizing theory and raises conceptual problems for evaluative maximization––difficulties in ranking mixes, problems with organic wholes, and mathematical versus internal evaluative judgments. As regards the evaluative decisions maximization is concerned with, it is argued that we are guided in our understanding of what is good by what is better. To the extent that the better is prior to the good, maximizations are parasitic on other evaluations. Concludes with a look at (...) the discussion of false pleasures in Plato's Philebus. (shrink)

People from one cultural background often find themselves wondering how those from a different cultural background could willingly live the way they do and/or criticize others for living in the way they do. How are we to explain this kind of mutual incomprehension? Three different possible explanations will be considered. The first is that such mutual incomprehension is sourced in a moral flaw. The flaw might be in one of the cultures, as certain cultures might be premised on a moral (...) mistake. Alternatively, the flaw might be a feature of the incomprehending individuals. If only they tried harder, they would come to appreciate the other’s point of view. The second possibility is that such mutual incomprehension is the product of principled limits on the interpretation of someone from another culture. Contrary to the first possibility, there might be no way for people from different cultures to even understand each other, let alone find fault in each other, because the culturally mediated ways in which they understand the world are inaccessible to each other. The third possibility is that the mutual incomprehension is sourced in metaphysics. Contrary to the second possibility, there might be some non-metaphorical sense in which people from different cultures inhabit different worlds. The main task of the chapter is to describe and evaluate these three possibilities with a view to ruling out the third. (shrink)