The first English translation of Fichte’s second set of 1804 lectures on the Wissenschaftslehre.

As improvements in neuroscience have enabled a better understanding of disorders of consciousness as well as methods to treat them, a hurdle that has become all too prevalent is the denial of coverage for treatment and rehabilitation services. In 2011, a settlement emerged from a Vermont District Court case, Jimmo v. Sebelius, which was brought to stop the use of an “improvement standard” that required tangible progress over an identifiable period of time for Medicare coverage of services. While the use (...) of this standard can have deleterious effects on those with many chronic conditions, it is especially burdensome for those in the minimally conscious state, where improvements are unpredictable and often not manifested through repeatable overt behaviors. Though the focus of this paper is on the challenges of brain injury and the minimally conscious state, which an estimated 100,000 to 200,000 individuals suffer from in the United States, the post-Jimmo arguments presented can and should have a broad impact as envisioned by the plaintiffs who brought the case on behalf of multiple advocacy groups representing patients with a range of chronic care conditions. (shrink)

This is the first article in a two-part series describing subject and family perspectives from the central thalamic deep brain stimulation for the treatment of traumatic brain injury using the Medtronic PC + S first-in-human invasive neurological device trial to achieve cognitive restoration in moderate to severe traumatic brain injury, with subjects who were deemed capable of providing voluntary informed consent. In this article, we report on interviews conducted prior to surgery wherein we asked participants about their experiences recovering from (...) brain injury and their perspectives on study enrollment and participation. We asked how risks and benefits were weighed, what their expectations and fears were, and how decisions were reached about trial participation. We found that informed consent and enrollment decisions are fraught. Subjects and families were often split, with subjects more focused on putative benefits and families concerned about incremental risk. Both subjects and families viewed brain injury as disruptive to personal identity and relationships. As decisions were made about study enrollment, families struggled with recognizing the re-emergent agency of subjects and ceding decision-making authority to subjects who had previously been dependent upon them for protection and guidance. Subjects and family members reported a hope for the relief of cognitive disabilities, improved quality of life, normalization of interpersonal interactions, and a return to work or school as reasons for study participation, along with altruism and a desire to advance science. Despite these aspirations, both subjects and families appreciated the risks of the intervention and did not suffer from a therapeutic misconception. A second essay to be published in the next issue of Cambridge Quarterly of Healthcare Ethics—Clinical Neuroethics will describe interviews conducted after surgery, the effects of cognitive restoration for subjects, families, and challenges presented to the social structures they will call upon to support them through recovery. This subsequent article will be available online prior to its formal publication in October 2023. (shrink)

There is some complementarity of models for the origin of the electroencephalogram (EEG) and neural network models for information storage in brainlike systems. From the EEG models of Freeman, of Nunez, and of the authors' group we argue that the wavelike processes revealed in the EEG exhibit linear and near-equilibrium dynamics at macroscopic scale, despite extremely nonlinear – probably chaotic – dynamics at microscopic scale. Simulations of cortical neuronal interactions at global and microscopic scales are then presented. The simulations depend (...) on anatomical and physiological estimates of synaptic densities, coupling symmetries, synaptic gain, dendritic time constants, and axonal delays. It is shown that the frequency content, wave velocities, frequency/wavenumber spectra and response to cortical activation of the electrocorticogram (ECoG) can be reproduced by a “lumped” simulation treating small cortical areas as single-function units. The corresponding cellular neural network simulation has properties that include those of attractor neural networks proposed by Amit and by Parisi. Within the simulations at both scales, sharp transitions occur between low and high cell firing rates. These transitions may form a basis for neural interactions across scale. To maintain overall cortical dynamics in the normal low firing-rate range, interactions between the cortex and the subcortical systems are required to prevent runaway global excitation. Thus, the interaction of cortex and subcortex via corticostriatal and related pathways may partly regulate global dynamics by a principle analogous to adiabatic control of artificial neural networks. (shrink)

This is the second paper in a two-part series describing subject and family perspectives from the CENTURY-S (CENtral Thalamic Deep Brain Stimulation for the Treatment of Traumatic Brain InjURY-Safety) first-in-human invasive neurological device trial to achieve cognitive restoration in moderate to severe traumatic brain injury (msTBI). To participate, subjects were independently assessed to formally establish decision-making capacity to provide voluntary informed consent. Here, we report on post-operative interviews conducted after a successful trial of thalamic stimulation. All five msTBI subjects met (...) a pre-selected primary endpoint of at least a 10% improvement in completion time on Trail-Making-Test Part B, a marker of executive function. We describe narrative responses of subjects and family members, refracted against that success. Interviews following surgery and the stimulation trial revealed the challenge of adaptation to improvements in cognitive function and emotional regulation as well as altered (and restored) relationships and family dynamics. These improvements exposed barriers to social reintegration made relevant by recoveries once thought inconceivable. The study’s success sparked concerns about post-trial access to implanted devices, financing of device maintenance, battery replacement, and on-going care. Most subjects and families identified the need for supportive counseling to adapt to the new trajectory of their lives. (shrink)

Amit's Hebbian model risks being overexplanatory, since it does not depend on specific physiological modelling of cortical ANNs, but concentrates on those phenomena which are modelled by a large class of ANNs. While offering a strong demonstration of the presence of Hebb's “cell assemblies,” it does not offer an equal account of Hebb's “phase sequence” concept.

We outline fresh findings that show that our macroscopic electrocorticographic (ECoG) simulations can account for synchronous multiunit pulse oscillations at separate, simultaneously activated cortical sites and the associated gamma-band ECoG activity. We clarify our views on the approximations of dynamic class applicable to neural events at macroscopic and microscopic scales, and the analogies drawn to classes of ANN behaviour. We accept the need to introduce memory processes and detailed anatomical and physiological information into any future developments of our simulations. On (...) the issue of intrinsic cortical stability and the role of extrinsic fibre systems in maintaining stability, we argue that this position is not in extreme contradiction to those of our commentators, and that the mechanisms implicit in our simulations' properties imply rich computational possibilities. We discuss some of the reasons for and against the existence of significant global resonances in the brain and explain why such behaviour appears absent in our simulations. Last, we discuss other phenomena, such as rhythmic driving of the cortex, which have not yet been introduced into our models, and indicate lines for future development of the simulations. (shrink)

_Feminist Interpretations of Thomas Hobbes _features the work of feminist scholars who are centrally engaged with Hobbes’s ideas and texts and who view Hobbes as an important touchstone in modern political thought. Bringing together scholars from the disciplines of philosophy, history, political theory, and English literature who embrace diverse theoretical and philosophical approaches and a range of feminist perspectives, this interdisciplinary collection aims to appeal to an audience of Hobbes scholars and nonspecialists alike. As a theorist whose trademark is a (...) compelling argument for absolute sovereignty, Hobbes may seem initially to have little to offer twenty-first-century feminist thought. Yet, as the contributors to this collection demonstrate, Hobbesian political thought provides fertile ground for feminist inquiry. Indeed, in engaging Hobbes, feminist theory engages with what is perhaps the clearest and most influential articulation of the foundational concepts and ideas associated with modernity: freedom, equality, human nature, authority, consent, coercion, political obligation, and citizenship. Aside from the editors, the contributors are Joanne Boucher, Karen Detlefsen, Karen Green, Wendy Gunther-Canada, Jane S. Jaquette, S. A. Lloyd, Su Fang Ng, Carole Pateman, Gordon Schochet, Quentin Skinner, and Susanne Sreedhar. (shrink)

The gap between the number of organs available for transplant and the number of individuals who need transplanted organs continues to increase. At the same time, thousands of transplantable organs are needlessly overlooked every year for the single reason that they come from individuals who were declared dead according to cardio pulmonary criteria. Expanding the donor population to individuals who die uncontrolled cardiac deaths will reduce this disparity, but only if organ preservation efforts are utilized. Concern about potential legal liability (...) for temporary preservation of organs pending a search for family members appears to be one of the impediments to wider use of donation in cases of uncontrolled cardiac death in states without statutes explicitly authorizing such action. However, we think that the risk of liability for organ preservation under these circumstances is de minimis, and that concerns about legal impediments to preservation should yield to the ethical imperative of undertaking it. (shrink)

In this paper, we assume that organ donation policy in the United States will continue to be based on an opt-in model, requiring express consent to donate, and that families will continue to have the prerogative to make donation decisions whenever the deceased person has not recorded his or her own preferences in advance. The limited question addressed here is what should be done when a potential donor dies unexpectedly, without any recorded expression of his or her wishes at hand, (...) while a family decision is being sought. (shrink)

An Eternity 1988 Book of the Year! Since its publication, the New Dictionary of Theology has rapidly established itself as a standard, authoritative reference work in systematic and historical theology. More than 630 articles cover a variety of theological themes, thinkers and movements: from creation to the millennium from Abelard to Zwingli from Third World liberation theology to South African Dutch Reformed theology Firmly anchored in the evangelical tradition, the NDOT is nevertheless wide-ranging in its scope. Over 200 contributors, experts (...) in their individual fields, offer both Western and international perspective. Concise and comprehensive, biblically grounded and historically informed, even-handed and free from unduly technical language, this dictionary has been praised by general readers, pastors and scholars. (shrink)

The glucocorticoid receptor belongs to an important class of transcription factors that alter the expression of target genes in response to a specific hormone signal. The glucocorticoid receptor can function at least at three levels: (1) recruitment of the general transcription machinery; (2) modulation of transcription factor action, independent of DNA binding, through direct protein‐protein interactions; and (3) modulation of chromatin structure to allow the assembly of other gene regulatory proteins and/or the general transcription machinery on the DNA. This review (...) will focus on the multifaceted nature of protein‐protein interactions involving the glucocorticoid receptor and basal transcription factors, coactivators and other transcription factors, occurring at these different levels of regulation. (shrink)

A role of perirhinal cortex (PrC) in recognition memory for objects has been well established. Contributions of parahippocampal cortex (PhC) to this function, while documented, remain less well understood. Here, we used fMRI to examine whether the organization of item-based recognition memory signals across these two structures is shaped by object category, independent of any difference in representing episodic context. Guided by research suggesting that PhC plays a critical role in processing landmarks, we focused on three categories of objects that (...) differ from each other in their landmark suitability as confirmed with behavioral ratings (buildings > trees > aircraft). Participants made item-based recognition-memory decisions for novel and previously studied objects from these categories, which were matched in accuracy. Multi-voxel pattern classification revealed category-specific item-recognition memory signals along the long axis of PrC and PhC, with no sharp functional boundaries between these structures. Memory signals for buildings were observed in the mid to posterior extent of PhC, signals for trees in anterior to posterior segments of PhC, and signals for aircraft in mid to posterior aspects of PrC and the anterior extent of PhC. Notably, item-based memory signals for the category with highest landmark suitability ratings were observed only in those posterior segments of PhC that also allowed for classification of landmark suitability of objects when memory status was held constant. These findings provide new evidence in support of the notion that item-based memory signals for objects are not limited to PrC, and that the organization of these signals along the longitudinal axis that crosses PrC and PhC can be captured with reference to landmark suitability. (shrink)

The development of theories of global cortical dynamics, using linear wave theory, owes much to the pioneering work of Nunez. His work leads to clear predictions on relations of brain size, axonal conduction velocity, and the frequencies of the cerebral rhythms. These predictions do not appear to be fulfilled, but their falsification constrains the range of parameters applicable in further formulations.

Freeman's pioneering work -- and neurodynamics in general -- has largely ignored specification of an anatomical framework within which features of coherent objects are represented, associated, deleted, and manipulated in computations. Recent theoretical work suggests such a framework can emerge during embryogenesis by selection of neuron ensembles and synaptic connections that maximize the magnitude of synchrony while approaching ultra-small-world connectivity. The emergent structures correspond to those of both columnar and non-columnar cortex. With initial connections thus organized, spatio-temporal information in sensory (...) inputs can generate systematic and specific patterns of synchronous oscillation, with consequent synaptic storage. The theoretical assemblies of connections resemble experimentally observed 'lego sets', while facilitation and interference among synchronous patterns, particularly when executed by fast synapses under metabolic entanglement, imply powerful parallel computation. (shrink)

This paper argues that the Food and Drug Administration’s (FDA) policy for health and wellness apps is ethically problematic. Currently, the FDA does not regulate health and wellness apps that are not intended for medical use. As a result of this hands‐off policy, preventing harm to consumers is left primarily to developers and app marketplaces. We argue that the FDA’s duties to prevent harm and maintain accountability to the American public require that they play a much stronger role. We also (...) discuss concerns about efficiency and fostering innovation, and argue that while they should help shape FDA regulation of health and wellness apps, they do not justify complete absence of FDA involvement. -/- . (shrink)

Consumers do not always follow their ideological beliefs about the need to engage in environmentally friendly consumption. We propose that Commitment to Beliefs —the general tendency to follow one’s value-based beliefs—can help identify who is most likely to follow their environmental ideologies. We predicted that CTB would amplify the effect of beliefs prescribing environmental stewardship, or neglect, on corresponding intentions, behavior, and purchasing decisions. In two studies, CTB amplified the positive and negative effects of relevant EF ideologies on EF purchase (...) decisions, and consumption and conservation attitudes, intentions, as well as future behavior. In each study, only people with higher levels of CTB demonstrated the most ideologically consistent consumption and conservation intentions and behavior. These findings clarify who is most likely to align their decisions and lifestyles according to their sustainable consumption ideologies. The amplification effect of CTB, and the CTB variable itself, present new contributions to consumer behavior research and the domains of sustainable or ethical consumption in particular and offer wide-ranging potential for marketing practitioners and researchers. (shrink)

Hypocretin regulates brain reward function and cocaine consumption in rats. The hypocretinergic (Hcrt) system is implicated in energy homeostasis, feeding and sleep regulation. Hypocretinergic cell bodies are located in the lateral hypothalamus (LH) and project throughout the brain. The aim of the present studies was to investigate the role of the Hcrt system in regulating brain reward function and the reinforcing properties of cocaine in rats. Intracranial self-stimulation (ICSS) thresholds provide an accurate measure of brain reward function in rats. Here (...) we show that a single injection of Hcrt-1 (5 µg icv) induced persistent, long-lasting elevations in ICSS thresholds in drug-naïve rats. Indeed, Hrct-1 elevated ICSS thresholds for 36 h, with peak elevations between 6 and 12 hours after injection. Hrct-1-induced threshold elevations were attenuated by an antibody known to neutralize the binding of hcrt-1 to its receptors. Taken together, these observations suggest that Hrct-1 negatively regulates brain reward function in rats. Because Hrct-1 negatively regulates brain reward function, we hypothesized that it may attenuate the increased brain reward function usually observed after cocaine consumption, and thereby alter cocaine self-administration behavior. A daily injection of Hrct-1 (1 µg icv), for 4 consecutive days, slightly increased cocaine self-administration (0.25 mg/infusion) in rats. Overall, these data demonstrate that Hrct-1 negatively regulates brain reward function, and as such may indirectly alter cocaine self-administration. Given the well-established role of hypocretin neurons in regulating feeding behavior and sleep, we hypothesize that hypocretinergic regulation of brain reward function may provide a mechanism by which appropriate and competing behaviors (e.g. sleep or feeding) may be engaged to maintain energy homeostasis. (shrink)

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)

A recent article in this journal described practical and conceptual difficulties faced by public health researchers studying scabies outbreaks in British residential care facilities. Their study population was elderly, decisionally incapacitated residents, many of whom lacked a legally appropriate decision-maker for healthcare decisions. The researchers reported difficulties securing Research Ethics Committee approval. As practicing healthcare ethicists working in a large Canadian research hospital, we are familiar with this challenge and welcomed the authors’ invitation to join the discussion of the ‘outstanding (...) ambiguities and further questions’ that their experience uncovered. We propose a Power of Attorney for Research as one substantive solution to help address the problems they identified. Although we acknowledge the familiar shortcomings associated with Advance Directives in the clinical context, we believe that Powers of Attorney for Research Participation, accompanied by Advance Research Directives, may increase the likelihood of gaining deeper understandings of potential participant’s values and priorities and how they might apply to foreseeable research opportunities. (shrink)