Dynamics of brain states and cortical excitability in paroxysmal neurological conditions

Epilepsy and migraine are neurological conditions that are characterised by periods of disruption of normal neuronal functioning. Aside from this paroxysmal feature, both conditions share genetic mutations and altered cortical excitability. People with epilepsy appear to be diagnosed with migraine more often than people without epilepsy and, likewise, people with migraine seem to be diagnosed with epilepsy more often than people without migraine. Changes in cortical excitability may help explain the pathophysiological link between both conditions, and could be a biomarker to monitor disease activity. In this thesis, the association between migraine and epilepsy and their relation to cortical excitability is further explored. A meta-analysis of previous population based studies provides epidemiological evidence for the co-occurrence of migraine and epilepsy. The combination of computer modelling with human electroencephalographic recordings offers insight into multi-stability of brain states in epilepsy. Results described in this thesis show that Transcranial Magnetic Stimulation can be used to measure cortical excitability, but that its use as a biomarker of disease activity in epilepsy is limited due to large interindividual variability. By combining Transcranial Magnetic Stimulation with electroencephalography, two novel variables that may contribute to cortical excitability are investigated: phase clustering, which possibly reflecting functional neuronal connectivity, and the non-linear residual of a stimulus-response curve, which may reflect brain state multi-stability. The results presented in this thesis suggest that the higher propensity to global synchronisation is not shared between epilepsy and migraine. These new variables have potential value to differentiate people with epilepsy, but not people with migraine, from normal controls

Mixed molybdenum and vanadium oxide nanoparticles with excellent high-power performance as Li-ion battery negative electrodes

Several nano-sized mixed molybdenum/vanadium oxide monoclinic solid solutions were synthesised using a continuous hydrothermal flow process and studied with a wide range of physical characterization techniques including X-ray photoelectron spectroscopy, X-ray diffraction, transmission electron microscopy and X-ray absorption spectroscopy. The nanomaterials were tested as anodes for Li-ion batteries in the potential range 0.05–3.00 V vs. Li/Li+. Samples with nominal formulas of Mo0.5V0.5O2 and Mo0.33V0.67O2 showed excellent performance, especially at high current rates, due to their highly pseudocapacitive charge storage mechanism. At a specific current of 10 A g−1, Mo0.5V0.5O2 and Mo0.33V0.67O2 showed specific capacities of ca. 200 and 170 mAh g−1, respectively. Mo0.5V0.5O2 also showed good cyclability, with a specific capacity of 480 mAh g−1 after 150 cycles at a specific current of 0.5 A g−1. For cyclic voltammetries conducted at high scan rates, pseudocapacitive charge storage contributed more than 90% to the total charge storage for both samples. The scalability of the synthesis technique and excellent electrochemical performance at high power, make these materials promising as negative electrode active materials for Li-ion batteries

Risk stratification by pre-operative cardiopulmonary exercise testing improves outcomes following elective abdominal aortic aneurysm surgery : a cohort study

Background: In 2009, the NHS evidence adoption center and National Institute for Health and Care Excellence (NICE) published a review of the use of endovascular aneurysm repair (EVAR) of abdominal aortic aneurysms (AAAs). They recommended the development of a risk-assessment tool to help identify AAA patients with greater or lesser risk of operative mortality and to contribute to mortality prediction. A low anaerobic threshold (AT), which is a reliable, objective measure of pre-operative cardiorespiratory fitness, as determined by pre-operative cardiopulmonary exercise testing (CPET) is associated with poor surgical outcomes for major abdominal surgery. We aimed to assess the impact of a CPET-based risk-stratification strategy upon perioperative mortality, length of stay and non-operative costs for elective (open and endovascular) infra-renal AAA patients. Methods: A retrospective cohort study was undertaken. Pre-operative CPET-based selection for elective surgical intervention was introduced in 2007. An anonymized cohort of 230 consecutive infra-renal AAA patients (2007 to 2011) was studied. A historical control group of 128 consecutive infra-renal AAA patients (2003 to 2007) was identified for comparison. Comparative analysis of demographic and outcome data for CPET-pass (AT ≥ 11 ml/kg/min), CPET-fail (AT < 11 ml/kg/min) and CPET-submaximal (no AT generated) subgroups with control subjects was performed. Primary outcomes included 30-day mortality, survival and length of stay (LOS); secondary outcomes were non-operative inpatient costs. Results: Of 230 subjects, 188 underwent CPET: CPET-pass n = 131, CPET-fail n = 35 and CPET-submaximal n = 22. When compared to the controls, CPET-pass patients exhibited reduced median total LOS (10 vs 13 days for open surgery, n = 74, P < 0.01 and 4 vs 6 days for EVAR, n = 29, P < 0.05), intensive therapy unit requirement (3 vs 4 days for open repair only, P < 0.001), non-operative costs (£5,387 vs £9,634 for open repair, P < 0.001) and perioperative mortality (2.7% vs 12.6% (odds ratio: 0.19) for open repair only, P < 0.05). CPET-stratified (open/endovascular) patients exhibited a mid-term survival benefit (P < 0.05). Conclusion: In this retrospective cohort study, a pre-operative AT > 11 ml/kg/min was associated with reduced perioperative mortality (open cases only), LOS, survival and inpatient costs (open and endovascular repair) for elective infra-renal AAA surgery

A neurophenomenological approach to non-ordinary states of consciousness: hypnosis, meditation, and psychedelics

Copyright © 2023 The Authors. No contemporary unifying framework has been provided for the study of non-ordinary states of consciousness (NSCs) despite increased interest in hypnosis, meditation, and psychedelics. NSCs induce shifts in experiential contents (what appears to the experiencer) and/or structure (how it appears). This can allow the investigation of the plastic and dynamic nature of experience from a multiscale perspective that includes mind, brain, body, and context. We propose a neurophenomenological (NP) approach to the study of NSCs which highlights their role as catalysts of transformation in clinical practice by refining our understanding of the relationships between experiential (subjective) and neural dynamics. We outline the ethical implications of the NP approach for standard conceptions of health and pathology as well as the crucial role of experience-based know-how in NSC-related research and application.This research was supported by Mind and Life Europe, the LABEX CORTEX of Université de Lyon (ANR-11-LABX-0042) within the 'Investissements d'Avenir' program (ANR-11-IDEX-0007) (to A.L.), by a European Research Council grant (ERC-Consolidator 617739-BRAINandMINDFULNESS) (A.L.), BIAL Foundation (260/16; P.R.B. and A.L.; Grant Nos 261/18 and 344/20 to O.G.), the EU Horizon 2020 Research and Innovation Program under Marie Skłodowska-Curie grant agreement 749582 (Neural Correlates of Self/NeuCoSe; P.R.B) and under the Specific Grant Agreement No. 945539 (Human Brain Project SGA3), University and University Hospital of Liège, Benoit Foundation (Bruxelles), and King's College London (King's Together Fund research grant 'Towards Experiential Neuroscience Paradigm'; E.A.), the Belgian Foundation Against Cancer (Grant Nos 2017064 and C/2020/1357), the Télévie, Wallonia as part of a program of the BioWin Health Cluster framework and the Swiss Neuromatrix Foundation (Grant No 2020-0201 to F.X.V.). C.T. is funded by donors of the Centre for Psychedelic Research; O.G. and S.L. are supported by the Fonds de la Recherche Scientifique (FRS)/Fonds National de la Recherche Scientifique (FNRS). The authors would like to thank Adeline Deward (RISE Illustration) for professional rendering of the figures

The Effective Lagrangian for Bulk Fermions in Models with Extra Dimensions

We compute the dimension 6 effective Lagrangian arising from the tree level integration of an arbitrary number of bulk fermions in models with warped extra dimensions. The coefficients of the effective operators are written in terms of simple integrals of the metric and are valid for arbitrary warp factors, with or without an infrared brane, and for a general Higgs profile. All relevant tree level fermion effects in electroweak and flavor observables can be computed using this effective Lagrangian.Comment: 22 pages. V2: typos corrected, matches published versio

Reducing Constraints in a Higher Dimensional Extension of the Randall and Sundrum Model

In order to investigate the phenomenological implications of warped spaces in more than five dimensions, we consider a $4+1+\delta$ dimensional extension to the Randall and Sundrum model in which the space is warped with respect to a single direction by the presence of an anisotropic bulk cosmological constant. The Einstein equations are solved, giving rise to a range of possible spaces in which the $\delta$ additional spaces are warped. Here we consider models in which the gauge fields are free to propagate into such spaces. After carrying out the Kaluza Klein (KK) decomposition of such fields it is found that the KK mass spectrum changes significantly depending on how the $\delta$ additional dimensions are warped. We proceed to compute the lower bound on the KK mass scale from electroweak observables for models with a bulk $SU(2)\times U(1)$ gauge symmetry and models with a bulk $SU(2)_R\times SU(2)_L\times U(1)$ gauge symmetry. It is found that in both cases the most favourable bounds are approximately $M_{KK}\gtrsim 2$ TeV, corresponding to a mass of the first gauge boson excitation of about 4-6 TeV. Hence additional warped dimensions offer a new way of reducing the constraints on the KK scale.Comment: 27 pages, 15 figures, v3: Additional comments in sections 1, 2 and 4. New appendix added. Five additional figures. References adde

The Fermion Mass Hierarchy in Models with Warped Extra Dimensions and a Bulk Higgs

The phenomenological implications of allowing the Higgs to propagate in both AdS${}_5$ and a class of asymptotically AdS spaces are considered. Without tuning, the vacuum expectation value (VEV) of the Higgs is peaked towards the IR tip of the space and hence such a scenario still offers a potential resolution to the gauge-hierarchy problem. When the exponent of the Higgs VEV is approximately two and one assumes order one Yukawa couplings, then the fermion Dirac mass term is found to range from $\sim 10^{-5}$ eV to $\sim 200$ GeV in approximate agreement with the observed fermion masses. However, this result is sensitive to the exponent of the Higgs VEV, which is a free parameter. This paper offers a number of phenomenological and theoretical motivations for considering an exponent of two to be the optimal value. In particular, the exponent is bounded from below by the Breitenlohner-Freedman bound and the requirement that the dual theory resolves the gauge hierarchy problem. While, in the model considered, if the exponent is too large, electroweak symmetry may not be broken. In addition, the holographic method is used to demonstrate, in generality, that the flatter the Higgs VEV, the smaller the contribution to the electroweak $T$ parameter. In addition, the constraints from a large class of gauge mediated and scalar mediated flavour changing neutral currents, will be at minimal values for flatter Higgs VEVs. Some initial steps are taken to investigate the physical scalar degrees of freedom that arise from a mixing between the $W_5/Z_5$ components and the Higgs components.Comment: 34 pages, 20 figures, 1 table; v3: matches version to be published in JHE