Mindfulness Meditation versus EEG-Alpha Neurofeedback: The Role of EEG-Alpha Enhancement in Attentional Control

This thesis directly compared two active interventions known to enhance the EEG-Alpha rhythm, mindfulness meditation (MM) with EEG-Alpha enhancement neurofeedback (NFB), relative to a non-active Sham-NFB control. Seventy-three university students were randomized to one of the three 15-minute single-session interventions. Participants were subsequently compared on their ability to enhance EEG-Alpha amplitude as well as regarding Stroop behavioural performance, EEG event-related potentials, and EEG-Alpha event-related desynchronization (ERD) as markers of attentional control. Participants randomized to MM, NFB, and Sham did not differ in their ability to modulate the EEG-Alpha rhythm post-intervention. However, enhancements in EEG-Alpha amplitude were seen within the MM and Alpha-NFB groups during these interventions. Participants randomized to MM and NFB exhibited reduced ERD during performance of the Stroop task, interpreted as reflecting reduced cognitive effort required for task performance. However, these were not accompanied by any group differences in Stroop behavioural performance or P300 amplitudes. This study provides preliminary support for the therapeutic potential of single-session treatments that target the EEG-Alpha rhythm, such as MM and NFB, to influence neural processes underlying attentional control. Further evaluation of the benefits of these interventions across multiple sessions is indicated

THE MANY WAYS OF WAKING UP FROM SLEEP - MOVING FORWARD THE ANALYSIS OF SLEEP MICROARCHITECTURE

One of the defining characteristics of sleep is that it is readily reversible towards wakefulness. This is exemplified in the common daily experience of waking up in the morning. My thesis studies sleep-wake transitions that are equally common and frequent, yet often not consciously perceived and neglected as random sleep perturbations of minor significance. Using mice as an experimental species, I find that healthy non-rapid-eye-movement sleep (NREMS), also named deep restorative sleep, is a dynamic brain state showing defined, periodically recurring moments of fragility. During these, diverse types of brief arousal-like events with various combinations of physiological correlates appear, including global or local cortical activation, muscle activity, and heart rate changes. Using a mice model of chronic neuropathic pain, I find that the rules I have identified in healthy sleep serve to identify previously unrecognized sleep disruptions that could contribute to sleep complaints of chronic pain patients. The experimental and analytical methods I have developed in these studies also helped in the identification of the neuronal basis of the fragility periods of NREM sleep. Together, my studies offer novel insights and analytical tools for the study of sleep-wake transitions and their perturbance in pathological conditions linked to sensory discomfort. More specifically, my work departed from recent findings that NREMS in mice is divided in recurring periods of sleep fragility at frequencies ~0.02 Hz, characterized by heightened arousability. Through analyzing the temporal distribution of brief arousal events termed microarousals, I hypothesized that these fragility periods could serve a time raster for the probing of spontaneous sleep perturbations. Motivated by the question of how sensory discomfort caused by pain affects sleep, I have used the spared nerve injury (SNI) model, which consists in the injury of two of the 3 branches of the sciatic nerve. I found that the role of fragility periods in timing spontaneous arousals is highly useful to identify sleep disruptions not commonly detected with standard polysomnographic measures. Thus, by scrutinizing the fragility periods of NREMS in the SNI mice, I discovered an overrepresentation of a novel form of local perturbation within the hindlimb primary somatosensory cortex (S1HL), accompanied by heart rate increases. In addition, I showed that SNI animals woke up more frequently facing external stimuli, using closed-loop methods targeting specifically the fragility or continuity periods. These findings led me to propose that chronic pain-related sleep complaints may arise primarily from a perturbed arousability. The closed-loop techniques to probe arousability could be transferred to interrogate neuronal mechanisms underlying NREMS fragility, leading to the recognition that intrusion of wake-related activity into NREMS is a previously underappreciated mechanism controlling sleep fragility and architecture. Overall, I present my thesis to advance the view on NREMS as a dynamic heterogeneous state of which insights into its neuronal mechanisms, and its physio- and pathophysiological manifestations in animal models should be key to formulate testable hypotheses aimed to cure the suffering of sleep disorder in human. -- Une des caractéristiques qui définit le sommeil, est que l’on peut rapidement retourner à un état d’éveil. De fait, nous l’expérimentons chaque matin au réveil. Ma thèse étudie les transitions sommeil-éveil qui, bien que fréquentes, sont souvent non consciemment perçues et traitées comme des perturbations sans importance et aléatoires du sommeil. En utilisant la souris comme modèle expérimental, je montre que le sommeil sans mouvements rapides des yeux (NREMS), également appelé le sommeil profond et réparateur, est un état cérébral dynamique composé de périodes discrètes et récurrentes de fragilité face à des stimuli externe. Pendant celles-ci, plusieurs types d’évènements associés à des éveils brefs apparaissent, combinant activation corticale, activité musculaire et/ou une hausse des battements cardiaques. Je démontre que la compréhension des transitions sommeil-éveil physiologiques s’avère utile pour étudier le sommeil de souris souffrant de douleurs neuropathiques chroniques. Ces souris présentent un nouveau type de perturbations locales lors du sommeil, qui pourraient possiblement expliquer une partie des plaintes de mauvais sommeil exprimées par les patients souffrant de douleurs chroniques. Les méthodes analytiques et expérimentales que j’ai développées dans ces études ont aussi aidé à l’identification des bases neuronales de la genèse des périodes de fragilités du sommeil NREM. En somme, mes études offrent des connaissances inédites et des méthodes d’analyses pour l’étude des transitions sommeil-éveil et de leurs perturbations en conditions pathologiques. Une étude récente du laboratoire a montré que le sommeil NREM est divisé en périodes de fragilité alternant avec des périodes de non-fragilité (continuité), environ toutes les 50 secondes ce qui donne une fréquence de 0.02 Hz. Les périodes de fragilité sont caractérisées par une hausse de « l’éveillabilité » ou propension à s’éveiller. Ma première observation est que les éveils brefs, couramment appelés micro-réveils, présentent une distribution temporelle hautement restreinte aux périodes de fragilité. Ainsi, j’ai émis l’hypothèse que ces périodes pourraient servir de moments spécialement choisis par le cerveau pour la mesure de potentielles perturbations spontanées. Motivé par la question de comment les douleurs chroniques perturbent le sommeil, je l’ai analysé chez un modèle de souris de douleurs neuropathique, le modèle de d’épargne du nerf sural (SNI). Le rôle des périodes de fragilité à restreindre les micro- réveils s’est avéré très utile pour détecter de nouvelles formes de réaction à des perturbations qui ne sont pas évidentes par des analyses classiques du sommeil. En effet, spécifiquement pendant ces périodes de fragilité, j’ai découvert une sur-représentation d’un nouveau type d’éveil local confiné au cortex somatosensoriel primaire et accompagné d’une hausse du rythme cardiaque. De plus, en utilisant de nouvelles méthodes basées sur des boucles-fermées, j’ai démontré que les souris SNI se réveillaient plus fréquemment que leurs contrôles en faisant face à des stimuli externes. Sur la base de ces découvertes, je propose que les plaintes de mauvais sommeil chez les patients souffrant de douleurs chroniques puissent prendre leur source dans une éveillabilité perturbée. Les méthodes de boucles-fermées pour analyser l’éveillabilité a aussi pu être transférée pour l’étude optogénétique des mécanismes neuronaux à la base de la fragilité du sommeil NREM. Cela a mené à la reconnaissance que l’intrusion d’activité normalement associée à l’éveil dans le sommeil est un mécanisme de contrôle de sa fragilité et de son architecture souvent ignoré dans le domaine. En somme, ma thèse permet une avancée de notre vision du sommeil NREM comme étant un état dynamique et hétérogène dont les mécanismes neuronaux sous-jacent, en conditions normales et pathogéniques, sont clefs pour la formulation d’hypothèses testables visant à la guérison des patients souffrant de troubles du sommeil

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

Syntax with oscillators and energy levels

This book presents a new approach to studying the syntax of human language, one which emphasizes how we think about time. Tilsen argues that many current theories are unsatisfactory because those theories conceptualize syntactic patterns with spatially arranged structures of objects. These object-structures are atemporal and do not lend well to reasoning about time. The book develops an alternative conceptual model in which oscillatory systems of various types interact with each other through coupling forces, and in which the relative energies of those systems are organized in particular ways. Tilsen emphasizes that the two primary mechanisms of the approach – oscillators and energy levels – require alternative ways of thinking about time. Furthermore, his theory leads to a new way of thinking about grammaticality and the recursive nature of language. The theory is applied to a variety of syntactic phenomena: word order, phrase structure, morphosyntax, constituency, case systems, ellipsis, anaphora, and islands. The book also presents a general program for the study of language in which the construction of linguistic theories is itself an object of theoretical analysis. Reviewed by John Goldsmith, Mark Gibson and an anonymous reviewer. Signed reports are openly available in the downloads session

Syntax with oscillators and energy levels

This book presents a new approach to studying the syntax of human language, one which emphasizes how we think about time. Tilsen argues that many current theories are unsatisfactory because those theories conceptualize syntactic patterns with spatially arranged structures of objects. These object-structures are atemporal and do not lend well to reasoning about time. The book develops an alternative conceptual model in which oscillatory systems of various types interact with each other through coupling forces, and in which the relative energies of those systems are organized in particular ways. Tilsen emphasizes that the two primary mechanisms of the approach – oscillators and energy levels – require alternative ways of thinking about time. Furthermore, his theory leads to a new way of thinking about grammaticality and the recursive nature of language. The theory is applied to a variety of syntactic phenomena: word order, phrase structure, morphosyntax, constituency, case systems, ellipsis, anaphora, and islands. The book also presents a general program for the study of language in which the construction of linguistic theories is itself an object of theoretical analysis. Reviewed by John Goldsmith, Mark Gibson and an anonymous reviewer. Signed reports are openly available in the downloads session

Syntax with oscillators and energy levels

This book presents a new approach to studying the syntax of human language, one which emphasizes how we think about time. Tilsen argues that many current theories are unsatisfactory because those theories conceptualize syntactic patterns with spatially arranged structures of objects. These object-structures are atemporal and do not lend well to reasoning about time. The book develops an alternative conceptual model in which oscillatory systems of various types interact with each other through coupling forces, and in which the relative energies of those systems are organized in particular ways. Tilsen emphasizes that the two primary mechanisms of the approach – oscillators and energy levels – require alternative ways of thinking about time. Furthermore, his theory leads to a new way of thinking about grammaticality and the recursive nature of language. The theory is applied to a variety of syntactic phenomena: word order, phrase structure, morphosyntax, constituency, case systems, ellipsis, anaphora, and islands. The book also presents a general program for the study of language in which the construction of linguistic theories is itself an object of theoretical analysis. Reviewed by John Goldsmith, Mark Gibson and an anonymous reviewer. Signed reports are openly available in the downloads session

Syntax with oscillators and energy levels

This book presents a new approach to studying the syntax of human language, one which emphasizes how we think about time. Tilsen argues that many current theories are unsatisfactory because those theories conceptualize syntactic patterns with spatially arranged structures of objects. These object-structures are atemporal and do not lend well to reasoning about time. The book develops an alternative conceptual model in which oscillatory systems of various types interact with each other through coupling forces, and in which the relative energies of those systems are organized in particular ways. Tilsen emphasizes that the two primary mechanisms of the approach – oscillators and energy levels – require alternative ways of thinking about time. Furthermore, his theory leads to a new way of thinking about grammaticality and the recursive nature of language. The theory is applied to a variety of syntactic phenomena: word order, phrase structure, morphosyntax, constituency, case systems, ellipsis, anaphora, and islands. The book also presents a general program for the study of language in which the construction of linguistic theories is itself an object of theoretical analysis. Reviewed by John Goldsmith, Mark Gibson and an anonymous reviewer. Signed reports are openly available in the downloads session

Syntax with oscillators and energy levels

This book presents a new approach to studying the syntax of human language, one which emphasizes how we think about time. Tilsen argues that many current theories are unsatisfactory because those theories conceptualize syntactic patterns with spatially arranged structures of objects. These object-structures are atemporal and do not lend well to reasoning about time. The book develops an alternative conceptual model in which oscillatory systems of various types interact with each other through coupling forces, and in which the relative energies of those systems are organized in particular ways. Tilsen emphasizes that the two primary mechanisms of the approach – oscillators and energy levels – require alternative ways of thinking about time. Furthermore, his theory leads to a new way of thinking about grammaticality and the recursive nature of language. The theory is applied to a variety of syntactic phenomena: word order, phrase structure, morphosyntax, constituency, case systems, ellipsis, anaphora, and islands. The book also presents a general program for the study of language in which the construction of linguistic theories is itself an object of theoretical analysis. Reviewed by John Goldsmith, Mark Gibson and an anonymous reviewer. Signed reports are openly available in the downloads session

Syntax with oscillators and energy levels

This book presents a new approach to studying the syntax of human language, one which emphasizes how we think about time. Tilsen argues that many current theories are unsatisfactory because those theories conceptualize syntactic patterns with spatially arranged structures of objects. These object-structures are atemporal and do not lend well to reasoning about time. The book develops an alternative conceptual model in which oscillatory systems of various types interact with each other through coupling forces, and in which the relative energies of those systems are organized in particular ways. Tilsen emphasizes that the two primary mechanisms of the approach – oscillators and energy levels – require alternative ways of thinking about time. Furthermore, his theory leads to a new way of thinking about grammaticality and the recursive nature of language. The theory is applied to a variety of syntactic phenomena: word order, phrase structure, morphosyntax, constituency, case systems, ellipsis, anaphora, and islands. The book also presents a general program for the study of language in which the construction of linguistic theories is itself an object of theoretical analysis. Reviewed by John Goldsmith, Mark Gibson and an anonymous reviewer. Signed reports are openly available in the downloads session