Surgical procedures of the brain and spine that require manipulation of, and near nervous structures, require unique considerations in their approach. Over the past 100 years, techniques have been developed and refined for localization of specific structures allowing for safer, more accurate interventions. These include the pre-operative use of Electroencephalography (EEG) in combination with radiographical imaging and intraoperative neurophysiological techniques rooted in electrophysiology. Since the introduction of EEG and electrical cortical stimulation, physicians have had the tools to diagnose neurological conditions while also being able to complete surgical interventions with a level of safety. By the 1920’s and 1930’s, the efforts of Hans Berger and Frederic and Erna Gibbs to develop and utilize EEG led to accurate pre-operative diagnoses of epilepsy along with their associated foci. Within that same time, the efforts of Wilder Penfield to develop and implement electrical cortical stimulation in awake patients during neurosurgery led to broad understandings of the organization and function of regions of the brain. Both EEG and cortical stimulation in combination quicky became useful beyond research in mapping the regions of the brain and led to rapid improvements in the accuracy of epilepsy surgery. Over preceding decades, these techniques continued to evolve with the latest research and technology. Additionally, their utilization has expanded from epilepsy surgery to resection for neoplasms of the central nervous system. In contemporary surgery, EEG and cortical stimulation still serve as the backbone of mapping techniques, but novel techniques are continually explored and improve patient outcomes. These advances include modern intraoperative neurophysiological monitoring, improved stimulation techniques, and additional utilization beyond the brain. This review highlights the conceptual underpinning of electrical neurophysiological mapping techniques as well as their implementation and future considerations. The review covers the pre-operative mapping of the brain using EEG, intraoperative mapping of the brain using cortical and subcortical mapping, and spinal cord mapping of the dorsal column and anterolateral tracts. The techniques and theory of each are summarized along with discussions on implementation and efficacy. Additional emphasis is placed on the need for standardization of their use to improve patient outcomes and recommendations for future research and development.

This thesis presents research aimed at elucidating neurophysiological and neuropsychological correlates of two psychiatric disorders, schizophrenia and PTSD. Although psychiatric disorders are not traditionally known for featuring cognitive deficits, research over the past three decades has revealed that deficits in many aspects of cognitive functioning are present across a wide range of disorders. Here, we aim to further our understanding of these deficits and provide evidence of the clinical utility of neurophysiological correlates of cognitive dysfunction. The cause and course of cognitive deficits in PTSD is poorly understood, and an investigation of one potential explanatory mechanism, dissociative symptomatology, is presented in the first part of this thesis. Our results suggest that dissociative symptomatology plays a role in cognitive dysfunction in PTSD, as among the clinical variables tested (including PTSD symptomatology, dissociative symptoms, depressive symptoms, and anxiety symptoms) dissociative symptoms were the only significantly correlated variables to cognitive dysfunction in a sample of combat-trauma exposed veterans with and without PTSD. In the second part of this thesis, we investigate the potential clinical utility of a neurophysiological biomarker for semantic processing deficits, the N400, in schizophrenia. Our results indicate that N400 measures are stable over a one week period and therefore may be clinically useful as a neurophysiological biomarker for semantic processing abnormalities in schizophrenia. Overall, these two studies contribute to our knowledge of cognitive deficits in psychiatric disorders and demonstrate their complexity as well as their potential to provide clinically useful tools to aid in the identification of novel treatments targeted at ameliorating cognitive deficits in schizophrenia and PTSD. / Thesis / Master of Science (MSc)

Objectives: To determine whether task-shifting the treatment of Postpartum depression (PPD) is effective in both treating mothers and mitigating the potential negative effects of PPD exposure on infant emotion regulation (ER). Methods: In Study 1, a randomized controlled trial (RCT) with a waitlist control group was used to examine whether a nine-week group Cognitive Behavioural Therapy (CBT) intervention delivered by peers can effectively treat PPD in mothers. Study 2 used data from this same RCT to determine if maternal PPD treatment with peer-delivered group CBT intervention would lead to adaptive change in markers of ER in their infants. Finally, Study 3 used data from a RCT with a treatment-as-usual control group to examine whether maternal treatment with a Public Health Nurse (PHN)-delivered group CBT intervention led to adaptive change in markers of infant ER. In both Studies 2 and 3, markers of infant ER included two neurophysiological measures and a maternal-report measure of infant temperament. Results: Study 1 found that peer-delivered group CBT led to significant improvements in symptoms of depression and anxiety in mothers and reductions in symptoms remained stable six months after treatment initiation. Study 2 found evidence of change in two neurophysiological measures of infant ER following maternal treatment with peer-delivered intervention, but not in the maternal-report measure of infant temperament. Finally, Study 3 found evidence of change in a single neurophysiological marker of infant ER following maternal treatment with the PHN-delivered intervention, but found no change following maternal treatment in a second neurophysiological marker and maternal-report measure of infant ER. Conclusions: The studies in this thesis highlight the potential of using task-shifting to fill a gap in the healthcare system’s treatment of PPD. This work suggests that interventions delivered by peers and PHNs may not only be effective in treating those with PPD, but may also benefit their infants by mitigating any PPD-related consequences on infant ER development. This thesis contributes to the evidence that suggests timely maternal treatment of PPD may disrupt the transmission of psychiatric risk from parent to infant. / Dissertation / Doctor of Philosophy (PhD) / Postpartum depression (PPD) is common and has consequences for both mothers and their infants. The negative impact of PPD exposure on infant emotion regulation (ER) is especially harmful because of its association with later psychopathology. As a result, the objectives of the present thesis were to i) determine whether task-shifting the treatment of PPD is effective in treating mothers while ii) mitigating the potential negative effects of PPD exposure on infant ER. The results of this thesis indicate that a task-shifted, peer-delivered treatment is effective in treating mothers with PPD and that treating mothers with a task-shifted treatment may also lead to adaptive changes in infant ER. This thesis indicates that task-shifting the treatment of PPD may improve outcomes for mothers, prevent PPD-related consequences on infant ER development, and ultimately, improve future outcomes for their infants.

Deliberate Emotion Regulation (ER), the effortful regulation of emotions, is strongly linked to psychopathology. In adults, deliberate ER is often experienced as a self-narrative, such as reappraising a negatively perceived scenario. However, researchers have yet to study how young children articulate deliberate ER strategies, whether these strategies relate to real-time ER neurophysiological processes, and how they are associated with psychopathology. Thus, from an existing sample of 59 children, I aimed to examine preschool-aged children’s verbally articulated ER strategies prior to a frustration challenge, and related these strategies to subsequent neural and physiological responses to frustration and psychopathology. I categorized children’s responses into two groups: those who articulated any emotion regulation strategy (i.e., “strategy”) and those who did not articulate a strategy (i.e., “no strategy”). We found that about 70% of children in this age range were able to articulate an emotion regulation strategy. Children who articulated a strategy had lower psychophysiological stress during a frustration task and fewer parent-reported ADHD inattention symptoms than children who did not articulate a strategy. There were no observed differences between groups for Prefrontal Cortex (PFC) activation, parent-reported externalizing symptoms, or parent-reported irritability symptoms. To our knowledge, this study is the first to provide evidence that emotion regulation strategy articulation is an emerging skill, and that children who are able to articulate emotion regulation strategies are also able to change their physiological stress in response to a negative emotion challenge and have fewer symptoms of psychopathology.

No description available.

In study one, the executive functioning of 19 high-functioning (HFA) and 19 low-functioning (LFA) children with ASD were compared to 28 children with normal development using a battery of neuropsychological tests. Results not only confirmed previous knowledge that children with ASD had significant executive dysfunctions compared with children with normal development, but also extended it to show that LFA children were significantly more impaired than HFA children. Study two built on this knowledge and examined whether immunological abnormalities are associated with the differential executive dysfunctions in 18 HFA and 19 LFA children. Results indicated that LFA children showed greater executive dysfunctions as well as higher levels of total lymphocyte, T lymphocyte and suppressor/cytotoxic T lymphocyte levels than HFA children. In addition, executive dysfunctions were significantly associated with the three lymphocyte levels, lending support to the notion that immunological factors may play a role in the cognitive dysfunctions in individuals with ASD. Study three further examined whether the differential executive dysfunctions and immunologic levels in LFA and HFA children are associated with their neural connectivity. Results on 17 HFA and 14 LFA children showed that LFA children had significantly elevated theta coherence in the anterior network, as well as at the left intra-hemispheric and right-to-left inter-hemisphere connections than HFA children. LFA children also had significantly elevated immunologic level specifically in suppressor/cytotoxic T lymphocytes. Furthermore, the executive dysfunctions, disordered neural connectivity, and abnormal immunologic levels were found to be associated. / Recent evidence suggests that deficient executive functions are fundamental to the cognitive deficits in Autism spectrum disorders (ASD). It has been suggested that individuals with ASD have disrupted neural connectivity including that in the frontal lobes that mediate executive functions. With reports of immunologic abnormalities in children with ASD, it is plausible that such abnormalities disrupt the neural connectivity in the brains of individuals with ASD. There is, however, relatively little empirical evidence to support the notion. This dissertation reports on three studies to examine whether the executive dysfunction in children with ASD is associated with their immunologic abnormalities and disordered neural connectivity. / These findings have provided some initial evidence to support the notion that immunologic factors may play a role in causing neuronal damage in the anterior region of the brains of children with ASD, which is manifested in their disordered neural connectivity of that region, and their executive dysfunctions mediated by that same region. / Han, Yvonne Ming Yee. / Adviser: Agnes Chan. / Source: Dissertation Abstracts International, Volume: 73-01, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves 103-132). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [201-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

Ma Ting. / "July 2004." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2004. / Includes bibliographical references (p. 181-196). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

GABA is the major inhibitory neurotransmitter in the central nervous system. It binds to two types of receptors –ionotropic GABAA and metabotropic GABAB. The GABAA receptor directly gates a Clionophore that causes hyperpolarization in mature excitatory neurons while GABAB receptor mediates a slower hyperpolarizing response via G-protein coupled receptor (GPCR) activated potassium channels. This signaling mechanism gets further complicated by the heterogeneous GABA receptor subunit composition that influences the response kinetics in the postsynaptic membrane. In this thesis, the focus has been to decipher the role of GABAA receptors in relation to cellular excitability in the subiculum under physiological and pathophysiological conditions. The subiculum, considered as the output structure of hippocampus, modulates information flow from hippocampus to various cortical and sub-cortical areas and has been implicated in learning and memory, rhythm generation and various neurological disorders. It gates hippocampal activity with its well orchestrated and fine tuned intrinsic and local network properties. Over the years many studies have shown the involvement of subiculum in temporal lobe epilepsy where it forms the focal point of epileptiform activities with altered cellular and network properties. The subiculum is characterized by the presence of a significant population of burst firing neurons that lead local epileptiform activity. By virtue of its bursting nature and recurrent connections, it is a potential site for seizure generation and maintenance. Epileptiform activities are dynamic in nature and change temporally and spatially according to the alterations in electrophysiological properties of neurons. Transitions to different electrical activities in neurons following a prolonged challenge with epileptogenic stimulus have been shown in other brain structures, but not in the subiculum. Considering the importance of the subicular burst firing neurons in the propagation of epileptiform activity to the entorhinal cortex, we have explored the phenomenon of electrophysiological phase transitions in the burst firing neurons of the subiculum in an in vitro brain slice model of epileptogenesis. Whole-cell patch clamp and extracellular field recordings revealed a distinct phenomenon in the subiculum wherein an early hyperexcitable phase was followed by a late suppressed phase upon continuous perfusion with epileptogenic 4-amino pyridine and magnesium-free medium. The late suppressed phase was characterized by inhibitory post-synaptic potentials (IPSPs) in pyramidal excitatory neurons and bursting activity in local fast spiking interneurons at a frequency of 0.1-0.8 Hz. The IPSPs were mediated by GABAA receptors that coincided with excitatory synaptic inputs to attenuate action potential discharge. These IPSPs ceased following a cut between the CA1 and subiculum. Our results suggest the importance of feedforward inhibition in the suppression of epileptiform activity in subiculum to mediate a homeostatic response towards the induced hyper-excitability. GABA release from presynaptic nerve endings activates postsynaptic GABAA receptors, which evoke faster phasic inhibitory postsynaptic currents (IPSCs) and non-inactivating inhibitory tonic current, mediated through extrasynaptic GABAA receptors. These receptors are heteropentameric GABA-gated channels assembled from 19 possible subunits (α1-6, β1-3, γ1-3, δ, π, ρ1-3, θ, and ε). The 2 major subunits involved in tonic GABAA currents in the hippocampus are α5 and δ subunits. Tonic GABAA receptor mediated inhibitory current plays an important role in neuronal physiology as well as pathophysiology such as mood disorders, insomnia, epilepsy, autism spectrum disorders and schizophrenia. While the alterations of various electrical properties due to tonic inhibition have been studied in neurons from different regions, its influence on intrinsic subthreshold resonance in pyramidal excitatory neurons having hyperpolarization-activated cyclic nucleotide-gated (HCN) channels is not known. In the present study, we show the involvement of α5βγ GABAA receptors in mediating picrotoxin sensitive tonic current in subicular pyramidal neurons using known pharmacological agents that target specific GABAA receptor subunits. We further investigated the contribution of tonic conductance in regulating subthreshold electrophysiological properties using current clamp and dynamic clamp experiments. Our experiments suggest that tonic GABAergic inhibition can actively modulate subthreshold properties of subicular pyramidal neurons including resonance due to HCNchannels that may potentially alter the response dynamics in an oscillating neuronal network.

<u><b>Introduction</u></b><p><p align = "justify">Les surdités cochléaires induisent, outre une audibilité réduite, une série de distorsions de la représentation neurale des sons. Deux des mécanismes à la base de ces distorsions sont d’une part une atteinte de la sélectivité fréquentielle et d’autre part des zones neuro-épithéliales non fonctionnelles. Tant le premier que le second mécanisme apparaissent dans une proportion variable et non prédictible d’un sujet à un autre. Deux tests permettent le diagnostic de ces atteintes spécifiques: la Courbe d’Accord (Tuning Curve: TC) et le Threshold Equalising Noise (TEN) test. La TC, mesurée par une technique psychoacoustique chez un adulte collaborant (Psychophysical TC: PTC), consiste en la mesure du niveau de bruit (masqueur) nécessaire pour masquer un son pur (signal) de fréquence et d’intensité fixes. Le TEN test consiste en la mesure des seuils auditifs dans le silence et en présence d’un bruit égalisateur de seuil (TEN). Ces tests qui requièrent des capacités cognitives adultes normales, ne sont pas applicables aux populations pédiatriques prélinguales.<p>Ce travail de thèse avait pour but le développement d’un équivalent objectif et non invasif des TCs et du TEN test applicable aux populations pédiatriques. La méthode objective choisie fut les potentiels auditifs stationnaires ou ASSEPs (Auditory Steady State Evoked Potentials). Les ASSEPs sont une réponse électrophysiologique cérébrale évoquée par un stimulus acoustique de longue durée modulé en amplitude et/ou en fréquence.</p align = "justify"><p><u><b>Méthodes & Résultats</u></b><p><p>Etape 1<p><p align = "justify">Les développements méthodologiques ont été réalisés sur l’espèce canine et humaine adulte. Les ASSEPs n’ayant jamais été préalablement enregistrés chez le chien, une première étape à consister à définir chez cette espèce les paramètres d’enregistrement optimaux (modulation en amplitude optimale) dont on sait qu’ils interagissent avec l’état veille-sommeil, avec la fréquence testée et probablement avec l’espèce animale investiguée. <p>A cette fin, les seuils auditifs obtenus chez 32 chiens à l’aide des ASSEPs ont été validés à cinq fréquences audiométriques par comparaison aux seuils obtenus avec les potentiels auditifs du tronc cérébral évoqués aux bouffées tonales. <p>Les seuils obtenus aux ASSEPs avec les paramètres optimaux d’enregistrement (légèrement différents des paramètres optimaux humains) étaient similaires à ceux obtenus aux bouffées tonales. <p>Ces résultats ont été publiés dans Clinical Neurophysiology (Markessis et al. 2006; 117: 1760-1771).</p align = "justify"><p>Etape 2<p><p align = "justify">La possibilité de mesurer des TCs à l’aide des ASSEPs (ASSEP-TCs) a été évaluée sur 10 chiens. Les données canines ont été comparées à des données de la littérature, çàd aux TC enregistrées chez d’autres espèces et avec d’autres méthodes. Des ASSEP-TCs ont également été enregistrées chez 7 humains adultes et confrontées aux PTCs obtenues chez les mêmes sujets. Les PTCs sont typiquement energistrées avec un signal sinusoïdal alors que le stimulus utilisé pour évoquer un ASSEP est une sinusoïde modulée en amplitude. L’effet des sinusoïdes modulées en amplitude sur les paramètres qualitatifs et quantitatifs des TCs a donc été évalué en comparant les PTCs obtenues avec un son pur et avec un son pur modulé en amplitude chez 10 humains adultes. <p>Les résultats ont révélé que les ASSEP-TCs enregistrées chez le chien et l’humain présentaient des paramètres qualitatifs et quantitatifs similaires respectivement à ceux décrits dans la littérature et aux PTCs. Par ailleurs, auncun effet des stimuli modulés en amplitude sur les paramètres des PTCs n’a été démontré.<p>Ces données ont été publiées dans Ear & Hearing (Markessis et al. 2009, 30: 43-53).</p align = "justify"><p>Etape 3<p><p align = "justify">Les ASSEP-TCs ont été validées chez 10 chiens en comparant les données aux TC enregistrées par électrocochléographie (Compound Action Potential TC: CAP-TC). Le masqueur utilisé pour les CAP-TCs est typiquement une sinusoïde alors que le masqueur utilisé pour les ASSEP-TCs est un bruit à bande étroite. Dès lors, une comparaison du type de masqueur (sinusoïde vs bruit à bande étroite) sur les paramètres des CAP-TCs et ASSEP-TCs a été réalisée chez 10 chiens.<p>Les ASSEP-TCs chez le chien se sont révélées qualitativement et quantitativement similaires aux CAP-TCs quel que soit le type de masqueur. Elles presentaient par ailleurs l’avantage d’être moins variables, plus précises et non invasives par rapport aux CAP-TCs. <p>Ces données ont été publiées dans International Journal of Audiology (Markessis et al. 2010, 49 ;455-62).</p align = "justify"><p>Etape 4<p><p align = "justify">Afin d’étudier la validité de la procédure à mettre en évidence des changements de sélectivité fréquentielle dus à une atteinte cochléaire, des ASSEP-TCs ont été obtenues chez 10 chiens cochléo-lésés suite à un trauma acoustique. Les Produits de Distorsion Acoustiques, les potentiels évoqués auditifs du tronc cérébral évoqués par un clic et les ASSEPs à cinq fréquences audiométriques ont été enregisrés afin de délimiter l’étendue de la lésion.<p>Les ASSEP-TCs ont été fortement altérées, mais pas comme attendu ni suggéré par les mesures fonctionnelles indiquant que le trauma acoustique a créé une lésion différente de celle espérée. <p>Cette étude doit être poursuivie, des lésions moins importantes créées et une validation histopathologique réalisée.</p align = "justify"><p>Etape 5<p><p align = "justify">Le TEN test a été mesuré à l’aide des ASSEPs (ASSEP-TEN) chez 12 adultes et cinq enfants normo-entendants. Les données adultes ont été confrontées aux données comportementales. L’effet des stimuli ASSEP (son pur modulé en amplitude) sur les TEN test a également été investigué en comparant les données comportementales obtenues avec une sinusoïde et avec une sinusoïde modulée en amplitude chez 24 adultes. <p>Les seuils masqués enregistrés aux ASSEPs étaient supérieurs à ceux mesurés par une épreuve comportementale. L’élévation des seuils masqués pose un problème potentiel de dynamique.<p>La procédure doit être testée chez des patients présentant une surdité cochléaire attendu que la différence entre les seuils auditifs mesurés aux ASSEPs et par une épreuve comportementale est moindre dans cette population. Dans la mesure où le problème de dynamique résiduelle persiste chez les patients malentendants, d’autres stimuli ou algorithmes d’enregistrement doivent être utilisés.</p align = "justify"><p>Etape 6<p><p align = "justify">Le TEN est un stimulus large bande. Il peut dès lors se révéler intolérable chez des patients présentant une atteinte auditive restreinte à une region fréquentielle. L’effet du filtrage du TEN sur les seuils et la sonie du TEN a été étudié chez 24 sujets normo-entendants et 35 patients présentant une perte cochléaire dans les hautes fréquences.<p>Le filtrage passe-haut du TEN s’est avéré être une solution satisfaisante.<p>Ces données ont été publiées dans International Journal of Audiology (Markessis et al. 2006; 45: 91-98).</p align = "justify"><p>Etape 7<p><p align = "justify">L’effet de l’intensité du TEN sur le diagnostic des zones neuro-épithéliales non fonctionnelles a été investigué chez 24 patients en mesurant les seuils masqués à quatre intensités de TEN différentes. La fiabilité du TEN test a également été évaluée. <p>Le TEN est une procédure fiable. L’intensité du TEN a affecté le diagnostic chez cinq patients. Ce résultat est interprété en termes de degré de l’atteinte du complexe neurosensoriel.<p>Ces données ont été publiées dans International Journal of Audiology (Markessis et al. 2009; 48: 55-62).</p align = "justify"><p><u><b>Conclusion</u></b><p><p align = "justify">Un algorithme permettant la mesure de TC et du TEN test objective à l’aide des ASSEPs a été développé. L’implémentation clinique de l’algorithme appliqué à l’enregistrement des CA paraît envisageable. Une importante étape de la corrélation entre modifications anatomiques (à l’aide de l’histopathologie) et physiologiques (ASSEP-TC et CAP-TC) est maintenant celle qui s’impose. Les données préliminaires obtenues sur le TEN test électrophysiologique chez des sujets normo-entendants suggèrent que son implémentation clinique puisse se heurter à un problème de dynamique si ce dernier est confirmé en présence de surdités cochléaires. Plusieurs pistes potentielles de solutions ont été avancées.</p align = "justify"> / Doctorat en Sciences biomédicales et pharmaceutiques / info:eu-repo/semantics/nonPublished

Pain is a personal subjective experience with physiological and psychological components and involves many complex processes. In 1965 Melzack and Wall proposed the influential gate control theory (GCT) of pain and, in general, this has been supported by subsequent research. This theory postulates that cells in the substantia gelatinosa, located within the spinal cord, act like a gate mechanism that modulates the flow of information through the spinal cord to the brain and thus impacts on the pain experience. The abundance of literature and experimental data that is available from pain research supports the development and testing of computational models for the simulation and exploration of the pain process. Despite the fact that pain is an ideal candidate for modeling, it is an area that has received little attention. One of the few published models (Britton and Skevington, 1989; Britton et al., 1996) translated the explicitness of the GCT and its well-defined architecture into a basic mathematical model. The aim of this research is to develop a biologically appropriate computational model of pain, capable of modelling both acute and chronic pain states, and describe applications and simulations appropriate to such a model. Therefore this research firstly replicates a mathematical model of pain (Britton and Skevington, 1989; Britton et al., 1996) to explore its adequacy and to assess its potential for further development. The original model is then developed and extended to produce a more biologically plausible representation of the pain processes involved in the Gate Control mechanism. The improvements in the computational model have enabled a clinically plausible simulation of a pain modulatory technique, transcutaneous electrical nerve stimulation (TENS), which validates the model’s representation of the GCT and provides insight into how pain modulation can occur. Other developments to this model show its unique ability to represent symptoms of chronic pain, such as allodynia and hyperalgesia, which are associated with pathological pain states developed through the loss of inhibition and glial cell activation