196 research outputs found

    Innovative neurophysiological mechanisms and technologies for VNS in refractory epilepsy

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    Premixed turbulent flame calculation

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    The importance of turbulent premixed flames in a variety of applications has led to a substantial amount of effort towards improving the understanding of these flames. Although these efforts have increased the understanding, many questions still remain. The use of direct numerical simulation (DNS) in solving these questions is examined

    Infrared neurostimulation in ex-vivo rat sciatic nerve using 1470 nm wavelength.

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    OBJECTIVE: To design and implement a setup for ex-vivo optical stimulation for exploring the effect of several key parameters (optical power and pulse duration), activation features (threshold, spatial selectivity) and recovery characteristics (repeated stimuli) in peripheral nerves. APPROACH: A nerve chamber allowing ex-vivo electrical and optical stimulation was designed and built. A 1470 nm light source was chosen to stimulate the nerve. A photodiode module was implemented for synchronization of the electrical and optical channels. MAIN RESULTS: Compound Neural Action Potentials (CNAPs) were successfully generated with infrared light pulses of 200-2000 µs duration and power in the range of 3-10 W. These parameters determine a radiant exposure for stimulation in the range 1.59-4.78 J/cm2. Recruitment curves were obtained by increasing durations at a constant power level. Neural activation threshold is reached at a mean radiant exposure of 3.16 ± 0.68 J/cm2 and mean pulse energy of 3.79 ± 0.72 mJ. Repetition rates of 2-10 Hz have been explored. In 8 out of 10 sciatic nerves, repeated light stimuli induced a sensitisation effect in that the CNAP amplitude progressively grows, representing an increasing number of recruited fibres. In 2 out of 10 sciatic nerves, CNAPs were composed of a succession of peaks corresponding to different conduction velocities. SIGNIFICANCE: The reported sensitisation effect could shed light on the mechanism underlying Infrared NeuroStimulation (INS). Our results suggest that, in sharp contrast with electrical stimuli, optical pulses could recruit slow fibres early on. This more physiological order of recruitment opens the perspective for specific neuromodulation of fibre population who remained poorly accessible until now. Short high-power light pulses at wavelengths below 1.5 µm offer interesting perspectives for neurostimulation

    How Is the Norepinephrine System Involved in the Antiepileptic Effects of Vagus Nerve Stimulation?

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    Vagus Nerve Stimulation (VNS) is an adjunctive treatment for patients suffering from inoperable drug-resistant epilepsy. Although a complete understanding of the mediators involved in the antiepileptic effects of VNS and their complex interactions is lacking, VNS is known to trigger the release of neurotransmitters that have seizure-suppressing effects. In particular, norepinephrine (NE) is a neurotransmitter that has been associated with the clinical effects of VNS by preventing seizure development and by inducing long-term plastic changes that could restore a normal function of the brain circuitry. However, the biological requisites to become responder to VNS are still unknown. In this review, we report evidence of the critical involvement of NE in the antiepileptic effects of VNS in rodents and humans. Moreover, we emphasize the hypothesis that the functional integrity of the noradrenergic system could be a determining factor to obtain clinical benefits from the therapy. Finally, encouraging avenues of research involving NE in VNS treatment are discussed. These could lead to the personalization of the stimulation parameters to maximize the antiepileptic effects and potentially improve the response rate to the therapy

    Analysing vagus nerve spontaneous activity using finite element modelling

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    Objective. Finite element modelling has been widely used to understand the effect of stimulation on the nerve fibres. Yet the literature on analysis of spontaneous nerve activity is much scarcer. In this study, we introduce a method based on a finite element model, to analyse spontaneous nerve activity with a typical bipolar electrode recording setup, enabling the identification of spontaneously active fibres. We applied our method to the vagus nerve, which plays a key role in refractory epilepsy. Approach. We developed a 3D model including dynamic action potential propagation, based on the vagus nerve geometry. The impact of key recording parameters – inter-electrode distance and temperature – and uncontrolled parameters – fibre size and position in the nerve – on the ability to discriminate active fibres were quantified. A specific algorithm was implemented to detect and classify action potentials from recordings and tested on six rats in vivo vagus nerve recordings. Main results. Fibre diameters can be discriminated if they are below 3 µm and 7 µm, respectively for inter-electrode distances of 2 mm and 4 mm. The impact of the position of the fibre inside the nerve on fibre diameter discrimination, is limited. The range of active fibres identified by modelling in the vagus nerve of rats is in agreement with ranges found at histology. Significance. The nerve fibre diameter, directly proportional to the action potential propagation velocity, is related to a specific physiological function. Estimating the source fibre diameter is thus essential to interpret neural recordings. Among many possible applications, the present method was developed in the context of a project to improve vagus nerve stimulation therapy for epilepsy

    Locus coeruleus features are linked to vagus nerve stimulation response in drug-resistant epilepsy

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    peer reviewedThe locus coeruleus–norepinephrine system is thought to be involved in the clinical effects of vagus nerve stimulation. This system is known to prevent seizure development and induce long-term plastic changes, particularly with the release of norepinephrine in the hippocampus. However, the requisites to become responder to the therapy and the mechanisms of action are still under investigation. Using MRI, we assessed the structural and functional characteristics of the locus coeruleus and microstructural properties of locus coeruleus-hippocampus white matter tracts in patients with drug-resistant epilepsy responding or not to the therapy. Twenty-three drug-resistant epileptic patients with cervical vagus nerve stimulation were recruited for this pilot study, including 13 responders or partial responders and 10 non-responders. A dedicated structural MRI acquisition allowed in vivo localization of the locus coeruleus and computation of its contrast (an accepted marker of LC integrity). Locus coeruleus activity was estimated using functional MRI during an auditory oddball task. Finally, multi-shell diffusion MRI was used to estimate the structural properties of locus coeruleus-hippocampus tracts. These characteristics were compared between responders/partial responders and non-responders and their association with therapy duration was also explored. In patients with a better response to the therapy, trends toward a lower activity and a higher contrast were found in the left medial and right caudal portions of the locus coeruleus, respectively. An increased locus coeruleus contrast, bilaterally over its medial portions, correlated with duration of the treatment. Finally, a higher integrity of locus coeruleus-hippocampus connections was found in patients with a better response to the treatment. These new insights into the neurobiology of vagus nerve stimulation may provide novel markers of the response to the treatment and may reflect neuroplasticity effects occurring in the brain following the implantation

    Turbulent plume dispersal

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    Textual Integrity and Coherence in the Qur'an: Repetition and Narrative Structure in Surat al-Baqara

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    This study addresses the riddle of al-Baqara’s internal organization, utilizing new insights from literary theory and Biblical Studies to identify the sura’s structure and unifying themes. It also explores the possible added value in approaching al-Baqara as a whole compositional unit, as opposed to a conglomeration of isolated verse-groups. The dissertation begins with a historical overview of coherence-related approaches, commencing with the classical naẓm- and munāsaba-discourses as observed in the writings of Jāḥiẓ, Bāqillānī, Biqā῾ī and others, and extending to the modern period and the work of scholars such as Amīn Aḥsan Iṣlāḥī, ῾Abd al-Muta῾āl al-Ṣa῾īdī, and Matthias Zahniser. This overview is followed by a discussion of methodology, locating this study within the reader-oriented, synchronic, intertextual approaches, and showing methodological parallels with Biblical Studies. A new reading framework for the sura is developed, utilizing in part some of the theories of the Russian literary theorist and philosopher, Mikhail Bakhtin. The sura’s structure is identified by means of analyzing its distinctive repetitions, a known structuring device in oral texts. Incremental inclusios, alternations and chiasms delineate al-Baqara’s compositional subunits. The overall structure of the sura emerges as chiastic, following the pattern ABC/B’C’A’/C’’B’’A’’, where A is a section having the character of a test, B a section containing instructions and C a story portraying primeval origins. The repetitions are of increasing length, the general escalating character of the devices focusing attention on the last panel (C’’B’’A’’). In a first reading, the central theme is identified by means of the sura’s Leitwort, a leading keyword distinguished by its special location, high concentration and even distribution within the sura. Reading the sura for what it reveals about the deity, the Leitwort, ‘guidance’, indicates a common theme of ‘God as guide’. In a second reading, the sura is read for its pedagogical content and the central theme becomes ‘first lesson in the new religion’. The added value in approaching the sura as a whole, as a totality, is in seeing how each theme is progressively developed and elaborated by every one of the sura’s various panels and how these themes hold the sura together as a unit.Ph

    Application of a Reynolds Stress Model to Engine-Like Flow Calculations

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