Minds and Brains, Sleep and Psychiatry

OBJECTIVE: This article offers a philosophical thesis for psychiatric disorders that rests upon some simple truths about the mind and brain. Specifically, it asks whether the dual aspect monism—that emerges from sleep research and theoretical neurobiology—can be applied to pathophysiology and psychopathology in psychiatry. METHODS: Our starting point is that the mind and brain are emergent aspects of the same (neuronal) dynamics; namely, the brain–mind. Our endpoint is that synaptic dysconnection syndromes inherit the same dual aspect; namely, aberrant inference or belief updating on the one hand, and a failure of neuromodulatory synaptic gain control on the other. We start with some basic considerations from sleep research that integrate the phenomenology of dreaming with the neurophysiology of sleep. RESULTS: We then leverage this treatment by treating the brain as an organ of inference. Our particular focus is on the role of precision (i.e., the representation of uncertainty) in belief updating and the accompanying synaptic mechanisms. CONCLUSIONS: Finally, we suggest a dual aspect approach—based upon belief updating (i.e., mind processes) and its neurophysiological implementation (i.e., brain processes)—has a wide explanatory compass for psychiatry and various movement disorders. This approach identifies the kind of pathophysiology that underwrites psychopathology—and points to certain psychotherapeutic and psychopharmacological targets, which may stand in mechanistic relation to each other

Why has the 'Pain Revolution' not occurred? An analysis of the competition between material semiotic translations of pain in a neoliberal age.

This thesis investigates the competition between different material-semiotic translations of pain in the period of neoliberalism. Moseley and Butler (2017) published a novel pain theory, which understands pain as emergent from a complex system, in which biological, psychological, and social elements interact. The "Pain Revolution" is a practical implementation of the theory, but this thesis uses the phrase to refer to a wider paradigm shift that is unrealised. This thesis synthesises actor-network theory, Bourdieusian field sociology and narrative theory, and describes a competition between different material-semiotic translations of pain. It demonstrates that Moseley and Butler’s theory has not become imbricated in the networks of major institutions and their translations of pain, nor become predominant in the pain field. To understand why, this thesis traces the coevolution, from the mid 19th century to 2020, of an “economy of responsibility” and a competition between different translations of pain. I establish that this economy of responsibility has been constituted through complex interactions between juridical, insurantial, and professional elements, and been coextensive with a network of body-mind dualism that evolved through liberal, welfare state, and neoliberal periods. We will find that the aforementioned institutions and their translations of pain align with and help to sustain a neoliberal version of an economy of responsibility and network of body-mind dualism. The Pain Revolution is shown to be incommensurable with the juridical, insurantial, and professional logics operating in these networks and so it has not become imbricated with them. I demonstrate that the pain field, rather than operating as a scientific subfield marked by closure and autonomy, has been open to the heteronomous logics of medical, legal and insurance fields. The Pain Revolution has not taken hold in the pain field because it does not fully align with these logics

Activation of the pro-resolving receptor Fpr2 attenuates inflammatory microglial activation

Poster number: P-T099 Theme: Neurodegenerative disorders & ageing Activation of the pro-resolving receptor Fpr2 reverses inflammatory microglial activation Authors: Edward S Wickstead - Life Science & Technology University of Westminster/Queen Mary University of London Inflammation is a major contributor to many neurodegenerative disease (Heneka et al. 2015). Microglia, as the resident immune cells of the brain and spinal cord, provide the first line of immunological defence, but can become deleterious when chronically activated, triggering extensive neuronal damage (Cunningham, 2013). Dampening or even reversing this activation may provide neuronal protection against chronic inflammatory damage. The aim of this study was to determine whether lipopolysaccharide (LPS)-induced inflammation could be abrogated through activation of the receptor Fpr2, known to play an important role in peripheral inflammatory resolution. Immortalised murine microglia (BV2 cell line) were stimulated with LPS (50ng/ml) for 1 hour prior to the treatment with one of two Fpr2 ligands, either Cpd43 or Quin-C1 (both 100nM), and production of nitric oxide (NO), tumour necrosis factor alpha (TNFα) and interleukin-10 (IL-10) were monitored after 24h and 48h. Treatment with either Fpr2 ligand significantly suppressed LPS-induced production of NO or TNFα after both 24h and 48h exposure, moreover Fpr2 ligand treatment significantly enhanced production of IL-10 48h post-LPS treatment. As we have previously shown Fpr2 to be coupled to a number of intracellular signaling pathways (Cooray et al. 2013), we investigated potential signaling responses. Western blot analysis revealed no activation of ERK1/2, but identified a rapid and potent activation of p38 MAP kinase in BV2 microglia following stimulation with Fpr2 ligands. Together, these data indicate the possibility of exploiting immunomodulatory strategies for the treatment of neurological diseases, and highlight in particular the important potential of resolution mechanisms as novel therapeutic targets in neuroinflammation. References Cooray SN et al. (2013). Proc Natl Acad Sci U S A 110: 18232-7. Cunningham C (2013). Glia 61: 71-90. Heneka MT et al. (2015). Lancet Neurol 14: 388-40

Good Research Practice in Non-Clinical Pharmacology and Biomedicine

This open access book, published under a CC BY 4.0 license in the Pubmed indexed book series Handbook of Experimental Pharmacology, provides up-to-date information on best practice to improve experimental design and quality of research in non-clinical pharmacology and biomedicine

Ranibizumab versus laser therapy for the treatment of very low birthweight infants with retinopathy of prematurity (RAINBOW): an open-label randomised controlled trial

BACKGROUND: Despite increasing worldwide use of anti-vascular endothelial growth factor agents for treatment of retinopathy of prematurity (ROP), there are few data on their ocular efficacy, the appropriate drug and dose, the need for retreatment, and the possibility of long-term systemic effects. We evaluated the efficacy and safety of intravitreal ranibizumab compared with laser therapy in treatment of ROP. METHODS: This randomised, open-label, superiority multicentre, three-arm, parallel group trial was done in 87 neonatal and ophthalmic centres in 26 countries. We screened infants with birthweight less than 1500 g who met criteria for treatment for retinopathy, and randomised patients equally (1:1:1) to receive a single bilateral intravitreal dose of ranibizumab 0·2 mg or ranibizumab 0·1 mg, or laser therapy. Individuals were stratified by disease zone and geographical region using computer interactive response technology. The primary outcome was survival with no active retinopathy, no unfavourable structural outcomes, or need for a different treatment modality at or before 24 weeks (two-sided α=0·05 for superiority of ranibizumab 0·2 mg against laser therapy). Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, NCT02375971. INTERPRETATION: Between Dec 31, 2015, and June 29, 2017, 225 participants (ranibizumab 0·2 mg n=74, ranibizumab 0·1 mg n=77, laser therapy n=74) were randomly assigned. Seven were withdrawn before treatment (n=1, n=1, n=5, respectively) and 17 did not complete follow-up to 24 weeks, including four deaths in each group. 214 infants were assessed for the primary outcome (n=70, n=76, n=68, respectively). Treatment success occurred in 56 (80%) of 70 infants receiving ranibizumab 0·2 mg compared with 57 (75%) of 76 infants receiving ranibizumab 0·1 mg and 45 (66%) of 68 infants after laser therapy. Using a hierarchical testing strategy, compared with laser therapy the odds ratio (OR) of treatment success following ranibizumab 0·2 mg was 2·19 (95% Cl 0·99-4·82, p=0·051), and following ranibizumab 0·1 mg was 1·57 (95% Cl 0·76-3·26); for ranibizumab 0·2 mg compared with 0·1 mg the OR was 1·35 (95% Cl 0·61-2·98). One infant had an unfavourable structural outcome following ranibizumab 0·2 mg, compared with five following ranibizumab 0·1 mg and seven after laser therapy. Death, serious and non-serious systemic adverse events, and ocular adverse events were evenly distributed between the three groups. FINDINGS: In the treatment of ROP, ranibizumab 0·2 mg might be superior to laser therapy, with fewer unfavourable ocular outcomes than laser therapy and with an acceptable 24-week safety profile. FUNDING: Novartis

The experience of absorption : comparison of the mental processes of meditation between emic yogic and etic neuroscientific perspectives on Ishvara Pranidhana meditation

textModernity has seen the exchange of ideas about cognition between western science and eastern meditation traditions. In particular, western ways of thinking about the natural world have infiltrated Indian theories of yoga. This intersection of ideas in the twentieth-century has resulted in a problematic trend to theorize yogic phenomena, including meditation, in scientific terms. These translations converge on explicating yogic processes within a context of advancing knowledge about the brain. This translational approach to bringing etic and emic perspectives together in the same framework results in interpretations of meditation that succumb to problems cognitive science faces at a broader level in theorizing cognition and mind-body interrelations. In this study, I take a different approach to bringing emic and etic perspectives together by placing a phenomenologically interpreted emic account of absorption (the meditative shift in consciousness) into dialogue with current scientific understandings of three central mental processes of meditation. Specifically, I analyze ways of conceptualizing attention, memory, and emotion, and their underlying mechanisms as posited in yoga and science, focusing on the problem of how each system interprets the reality of absorption. This comparison suggests a basic similarity between the two systems: theorizing cognition and meditative absorption in terms of embodiment. This finding emphasizes the dual nature of embodiment as both experiential and physical. Finally, I consider this dialogue from an embodied mind perspective, an emerging way of thinking about and theorizing the mind-body in cognitive science, because this perspective challenges longstanding theoretical problems in western understandings of how the mind works. This analysis suggests that theorizing meditation in these dual terms of embodiment potentially solves the reductive challenges of dualistic and materialist philosophy that have plagued both religious and naturalistic attempts to explain absorption. This interdisciplinary dialogue provides a framework with which to think more critically about translational and cross-disciplinary efforts that have previously confused the goals of yoga and science and their respective foci on practice and mechanisms. I conclude that bridging ideas in this dialogical way reveals a complementary perspective between phenomenological and biological ways of understanding the mind that both hinge on embodied cognition.Educational Psycholog

READING NEUROSCIENCE: VENTRILOQUISM AS A METAPHOR FOR MULTIPLE READINGS OF SELF

This thesis argues that the consensus models of self forwarded and upheld in the fields of discourse most concerned with its description, indicate a process of ventriloquism where agency slips between dual poles of body and mind and cannot be tracked to a hiding place. Just as with ventriloquism, in these models of self it is unclear who is doing the 'talking', and the skill of performance would seem to make the distinction almost redundant. The self seems a complicity of often conflicting agents when analysed as its constituent parts, and not there at all when viewed as a whole. This thesis takes as its starting point the confusion of Edgar Bergen when struggling to justify his philosophical conversations with his dummy: who is at work here, and where would agency reside in such a dialogue? That it serves us to assume the 'theory of mind' explanation for the behaviours of others, and by extension place ourselves within a scaffold of causal motives, says more for the use value of such a theory than for the presence of 'mind'. Why this 'theory of mind' rather than any other? Because that is how mind and motive are presented to us during our acquisition of a spoken language. Mediation, transformation and referral: this thesis argues that these are qualities which characterize ventriloquism, and also the human means of perception and self-perception. There are a number of unfulfilled potentialities that reach their heaven in the unified self. The 'drive' to unity culls these lost futures and condemns us to another fulfilment, that of'oneness'. Most of these resolutions regarding self are predicated on what is 'in' and what is 'out'; how does the discriminatory self establish grounds for inclusivity or exclusivity? This thesis means to provide a lexicon of other possibilities regarding the conceptualization of self