Knowing Groundlessness: An Enactive Approach to a Shift From Cognition to Non-Dual Awareness

The enactive approach has become an influential paradigm in cognitive science. One of its most important claims is that cognition is sense-making: to cognize is to enact a world of meaning. Thus, a world is not pregiven but enacted through sense-making. Most importantly, sense-making is not a fixed process or thing. It does not have substantial existence. Instead, it is groundless: it springs from a dynamic of relations, without substantial ground. Thereby, as all cognition is groundless, this groundlessness is considered the central underlying principle of cognition. This article takes that key concept of the enactive approach and argues that it is not only a theoretical statement. Rather, groundlessness is directly accessible in lived experience. The two guiding questions of this article concern that lived experience of groundlessness: (1) What is it to know groundlessness? (2) How can one know groundlessness? Accordingly, it elaborates (1) how this knowing of groundlessness fits into the theoretical framework of the enactive approach. Also, it describes (2) how it can be directly experienced when certain requirements are met. In an additional reflexive analysis, the context-dependency and observer-relativity of those statements themselves is highlighted. Through those steps, this article exhibits the importance of knowing groundlessness for a cognitive science discourse: this underlying groundlessness is not only the “ground” of cognition, but it also can be investigated empirically through lived experience. However, it requires a methodology that is radically different from classical cognitive science. This article ends with envisioning a future praxis of cognitive science which enables researchers to investigate not only theoretically but empirically the “foundationless foundation” of cognition: groundlessness

Knowing the Knowing. Non-dual Meditative Practice From an Enactive Perspective

Within a variety of contemplative traditions, non-dual-oriented practices were developed to evoke an experiential shift into a mode of experiencing in which the cognitive structures of self-other and subject–object subside. These practices serve to de-reify the enactment of an observing witness which is usually experienced as separate from the objects of awareness. While several contemplative traditions, such as Zen, Mahāmudrā, Dzogchen, and Advaita Vedanta emphasize the importance of such a non-dual insight for the cultivation of genuine wellbeing, only very few attempts in contemplative science have turned toward the study of non-dual-oriented practices. This article starts from a recently developed theoretical cognitive science framework that models the requirements of a temporary experiential shift into a mode of experiencing free from cognitive subject–object structure. This model inspired by the enactive approach contributes theoretically grounded hypotheses for the much-needed rigorous study of non-dual practices and non-dual experiences. To do so, three steps are taken: first, common elements of non-dual-oriented practices are outlined. Second, the main ideas of enactive cognitive science are presented including a principled theoretical model of what is required for a shift to a pure non-dual experience, that is, an experiential mode that is unbound by subject–object duality. Third, this synthesized theoretical model of the requirements for the recognition of the non-dual is then compared with a specific non-dual style of meditation practice, namely, Mahāmudrā practice from Tibetan Buddhism. This third step represents a heuristic for evaluating the external coherence of the presented model. With this, the aim is to point toward a principled enactive view of non-dual meditative practice. In drawing the implications of the presented model, this article ends with an outlook toward next steps for further developing a research agenda that may fully address the concrete elements of non-dual practices

Towards new concepts for a biological neuroscience of consciousness

In the search for a sound model of consciousness, we aim at introducing new concepts: closure, compositionality, biobranes and autobranes. This is important to overcome reductionism and to bring life back into the neuroscience of consciousness. Using these definitions, we conjecture that consciousness co-arises with the non-trivial composition of biological closure in the form of biobranes and autobranes: conscious processes generate closed activity at various levels and are, in turn, themselves, supported by biobranes and autobranes. This approach leads to a non-reductionist biological and simultaneously phenomenological theory of conscious experience, giving new perspectives for a science of consciousness. Future works will implement experimental definitions and computational simulations to characterize these dynamical biobranes interacting

Surgical management of giant pituitary neuroendocrine tumors: Meta-analysis and consensus statement on behalf of the EANS skull base section.

The optimal surgical treatment for giant pituitary neuroendocrine tumors(GPitNETs) is debated. The aim of this paper is to optimize the surgical management of these patients and to provide a consensus statement on behalf of the EANS Skull Base Section. We constituted a task force belonging to the EANS skull base committee to define some principles for the management of GPitNETs. A systematic review was performed according to PRISMA guidelines to perform a meta-analysis on surgical series of GPitNETs. Weighted summary rates were obtained for the pooled extent of resection and according to the surgical technique. These data were discussed to obtain recommendations after evaluation of the selected articles and discussion among the experts. 20articles were included in our meta-analysis, for a total of 1263 patients. The endoscopic endonasal technique was used in 40.3% of cases, the microscopic endonasal approach in 34% of cases, transcranial approaches in 18.7% and combined approaches in 7% of cases. No difference in terms of gross total resection (GTR) rate was observed among the different techniques. Pooled GTR rate was 36.6%, while a near total resection (NTR) was possible in 45.2% of cases. Cavernous sinus invasion was associated with a lower GTR rate (OR: 0.061). After surgery, 35% of patients had endocrinological improvement and 75.6% had visual improvement. Recurrent tumors were reported in 10% of cases. After formal discussion in the working group, we recommend the treatment of G-PitNETs tumors with a more complex and multilobular structure in tertiary care centers. The endoscopic endonasal approach is the first option of treatment and extended approaches should be planned according to extension, morphology and consistency of the lesion. Transcranial approaches play a role in selected cases, with a multicompartmental morphology, subarachnoid invasion and extension lateral to the internal carotid artery and in the management of residual tumor apoplexy

Intracranial Aneurysm Classifier Using Phenotypic Factors: An International Pooled Analysis

Intracranial aneurysms (IAs) are usually asymptomatic with a low risk of rupture, but consequences of aneurysmal subarachnoid hemorrhage (aSAH) are severe. Identifying IAs at risk of rupture has important clinical and socio-economic consequences. The goal of this study was to assess the effect of patient and IA characteristics on the likelihood of IA being diagnosed incidentally versus ruptured. Patients were recruited at 21 international centers. Seven phenotypic patient characteristics and three IA characteristics were recorded. The analyzed cohort included 7992 patients. Multivariate analysis demonstrated that: (1) IA location is the strongest factor associated with IA rupture status at diagnosis; (2) Risk factor awareness (hypertension, smoking) increases the likelihood of being diagnosed with unruptured IA; (3) Patients with ruptured IAs in high-risk locations tend to be older, and their IAs are smaller; (4) Smokers with ruptured IAs tend to be younger, and their IAs are larger; (5) Female patients with ruptured IAs tend to be older, and their IAs are smaller; (6) IA size and age at rupture correlate. The assessment of associations regarding patient and IA characteristics with IA rupture allows us to refine IA disease models and provide data to develop risk instruments for clinicians to support personalized decision-making

Knowing groundlessness

Der Enactive Approach hat sich in den letzten Jahrzehnten zunehmend in der Kognitionswissenschaft etabliert. Seine zentrale Grundannahme ist, dass Kognition ein Prozess ist, in dem ein Lebewesen eine Welt hervorbringt. Bedeutung ist somit nicht „da draußen“ in einer bereits vorhandenen Welt, die lediglich abgebildet wird. Vielmehr wird Bedeutung erst hervorgebracht im Prozess der Kognition eines Lebewesens. Hierbei ist zu betonen, dass Kognition keine substanzielle Eigenexistenz hat. Kognition ist „leer“, ohne Fundament: Sie entspringt einer Dynamik von wechselseitigen Beziehungen zwischen vielen interdependenten Prozessen. Somit ist jeder Prozess der Kognition fundamentlos. Diese Fundamentlosigkeit, Leere oder Bodenlosigkeit liegt jeder Kognition „zugrunde“. Als Ausgangspunkt der vorliegenden Masterarbeit wird dieses zentrale Konzept der Boden-losigkeit aus dem Enactive Approach aufgegriffen und gezeigt, dass es nicht bloß ein philosophisch-abstraktes Konzept darstellt. Vielmehr verweist diese Idee der Bodenlosigkeit darüber hinaus auf eine bestimmte gelebte Erfahrung. Diesem Ausgangspunkt folgen die zwei Leitfragen dieser Masterarbeit: (1) Was ist das Erkennen von Bodenlosigkeit? (2) Wie kann Bodenlosigkeit erkannt werden? Zur Beantwortung dieser beiden Fragen wird zum einen erläutert, wie dieses Erkennen von Bodenlosigkeit im Zusammenhang zum Enactive Approach zu verstehen ist. Zum anderen wird der Prozess beschrieben, durch den dieses Erkennen von Bodenlosigkeit ermöglicht wird. In einer zusätzlichen reflexiven Analyse werden die Kontextabhängigkeit und BeobachterInnen-Relativität von Aussagen transparent gemacht und deren weitreichende Implikationen diskutiert. In einem nächsten Schritt wird die aus dem vorausgehenden Schritt resultierende theoreti-sche Beschreibung eines Übergangs von Kognition hin zum Erkennen von Bodenlosigkeit verglichen mit Übungsanleitungen aus der buddhistischen Mahāmudrā-Tradition sowie mit der phänomenologischen Reduktion. Aus diesem Vergleich geht die Schlussfolgerung hervor, dass die aus der Theorie abgeleiteten Vorhersagen darüber, was ein Übergang von Kognition zum Erkennen von Bodenlosigkeit erfordert, in enger Übereinstimmung damit steht, was Mahāmudrā-Praktizierende tun, um dieses Erkennen von Bodenlosigkeit in ihrer direkten Erfahrung zu ermöglichen. Auf diese Weise stellt die vorliegende Masterarbeit die Relevanz heraus, die das Erkennen von Bodenlosigkeit für einen kognitionswissenschaftlichen Diskurs hat: diese „zugrundeliegende“ Bodenlosigkeit ist nicht nur das „Fundament“ von Kognition, sondern wird darüber hinaus auch empirisch zugänglich gemacht durch die hier beschriebene Möglichkeit, sie direkt zu erkennen. Jedoch erfordert eine solche empirische Erforschung von Bodenlosigkeit eine Methode, die sich radikal von derjenigen der klassischen Kognitionswissenschaft unterscheidet. Abschließend stellt diese Masterarbeit die Vision eines zukünftigen Paradigmas in der Kognitionswissenschaft vor, welches eine empirische statt rein-theoretische Erforschung des „fundamentlosen Fundaments“ von Kognition ermöglicht: Bodenlosigkeit.The enactive approach has become an influential paradigm in cognitive science. One of its most important claims is that cognition is sense-making: to cognize is to enact a world of meaning. Thus, a world is not pregiven but enacted through sense-making. Most importantly, sense-making is not a fixed process or thing. It does not have substantial existence. Instead, it is groundless: it springs from a dynamic of relations, without substantial ground. Thereby, as all cognition is groundless, this groundlessness is considered the central underlying principle of cognition. This thesis takes that key concept of the enactive approach and argues that it is not only a theoretical statement. Rather, groundlessness is directly accessible in lived experience. The two guiding questions of this thesis concern that lived experience of groundlessness: (1) What is it to know groundlessness? (2) How can one know groundlessness? Accordingly, it elaborates (1) how this knowing of groundlessness fits into the theoretical framework of the enactive approach. Also, it describes (2) how it can be directly experienced when certain requirements are met. In an additional reflexive analysis, the context-dependency and ob-server-relativity of those statements themselves is highlighted. In a next step, the provided theory of a transition to knowing groundlessness is compared to practice instructions of the Buddhist Mahāmudrā tradition and to the process of the phenomenological reduction. As a result of this comparison, this thesis’ theoretical predictions of what a shift to knowing groundlessness requires turns out to be in close alignment with what Buddhist Mahāmudrā practitioners in fact do in order to enable experiences of groundlessness. Through those steps, this thesis exhibits the importance of knowing groundlessness for a cognitive science discourse: this underlying groundlessness is not only the “ground" of cognition, but it also can be investigated empirically through lived experience. However, it requires a methodology that is radically different from classical cognitive science. This thesis ends with envisioning a future praxis of cognitive science which enables researchers to investigate not only theoretically but empirically the “foundationless foundation” of cognition: groundlessness

Incorporation of charged residues in the CYP2J2 F-G loop disrupts CYP2J2–lipid bilayer interactions

AbstractCYP2J2 epoxygenase is an extrahepatic, membrane bound cytochrome P450 (CYP) that is primarily found in the heart and mediates endogenous fatty acid metabolism. CYP2J2 interacts with membranes through an N-terminal anchor and various non-contiguous hydrophobic residues. The molecular details of the motifs that mediate membrane interactions are complex and not fully understood. To gain better insights of these complex protein–lipid interactions, we employed molecular dynamics (MD) simulations using a highly mobile membrane mimetic (HMMM) model that enabled multiple independent spontaneous membrane binding events to be captured. Simulations revealed that CYP2J2 engages with the membrane at the F-G loop through hydrophobic residues Trp-235, Ille-236, and Phe-239. To explore the role of these residues, three F-G loop mutants were modeled from the truncated CYP2J2 construct (Δ34) which included Δ34-I236D, Δ34-F239H and Δ34-I236D/F239H. Using the HMMM coordinates of CYP2J2, the simulations were extended to a full POPC membrane which showed a significant decrease in the depth of insertion for each of the F-G loop mutants. The CYP2J2 F-G loop mutants were expressed in E. coli and were shown to be localized to the cytosolic fraction at a greater percentage relative to construct Δ34. Notably, the functional data demonstrated that the double mutant, Δ34-I236D/F239H, maintained native-like enzymatic activity. The membrane insertion characteristics were examined by monitoring CYP2J2 Trp-quenching fluorescence spectroscopy upon binding nanodiscs containing pyrene phospholipids. Relative to the Δ34 construct, the F-G loop mutants exhibited lower Trp quenching and membrane insertion. Taken together, the results suggest that the mutants exhibit a different membrane topology in agreement with the MD simulations and provide important evidence towards the involvement of key residues in the F-G loop of CYP2J2

Surgical management of Tuberculum sellae Meningiomas: Myths, facts, and controversies.

The optimal management of tuberculum sellae (TS) meningiomas, especially the surgical strategy, continues to be debated along with several controversies that persist. A task force was created by the EANS skull base section committee along with its members and other renowned experts in the field to generate recommendations for the surgical management of these tumors on a European perspective. To achieve this, the task force also reviewed in detail the literature in this field and had formal discussions within the group. The constituted task force dealt with the practice patterns that exist with respect to pre-operative radiological investigations, ophthalmological and endocrinological assessments, optimal surgical strategies, and follow-up management. This article represents the consensually derived opinion of the task force with respect to the surgical treatment of tuberculum sellae meningiomas. Areas of uncertainty where further clinical research is required were identified