title: Theoretical and experimental investigation of anaesthetic effects in the brain

authors: Noroozbabaee, Leyla

abstract: The main motivation of this study is to develop a better understanding of anaesthetic drug effects on brain dynamics including the paradoxical enhancement of seizure activity by some anaesthetic drugs. This thesis investigates two mean-field descriptions for the effect of general anaesthetic agents on brain activity: the extended Waikato cortical model (WM) and the Hindriks and van Putten (HvP) thalamocortical model. In the standard Waikato model, the population-average neuron voltage is determined by incoming activity at both electrical (gap-junction) and chemical synapses, the latter mediated by AMPA (excitatory) and GABAA (inhibitory) receptors. Here we extend the standard WM by including NMDA (excitatory) and GABAB (inhibitory) synapses. GABAergic anaesthetics, such as propofol, boost cortical inhibition by prolonging the tail of the unitary IPSP (inhibitory postsynaptic potential) at GABAA receptors, while increasing the synaptic gain at the slower-acting GABAB receptors. Dissociative anaesthetics act on NMDA receptors to give a voltage-dependent alteration of excitatory synaptic gain. We find that increasing GABAB or NMDA effect can alter the spatiotemporal dynamics of the standard WM, tending to suppress spatial (Turing) patterns in favour of temporal (Hopf) oscillations. The extended WM predicts increased susceptibility to seizure when GABAB effect is increased, particularly if the GABAergic agent reduces gap-junction diffusion. 
We tested these WM predictions with two biological experiments. We found that potentiation of GABAB receptors in slices of mouse cortical tissue tended to enhance seizure-like activity. However, our in vivo investigation of the effect of closure of gap junctions did not reveal any seizure patterns in mouse EEG signals. 
In the second part of this thesis, we present a detailed analysis of the HvP thalamocortical mean-field model for propofol anaesthesia. While we were able to confirm the Hindriks and van Putten predictions of increases in delta and alpha power at low levels of anaesthetic sedation, we find that for deeper anaesthetic effect, the model jumps from the low-firing state to an extremely high-firing stable state (~250 spikes/s), and remains stuck there even at GABAA prolongations as high as 300% which would be expected to induce full comatose suppression of all firing activity. To overcome this pathological behaviour, we tested two possible modifications: first, eliminating the population-dependent anaesthetic sensitivity (efficacy) of the HvP model; second, incorporating reversal potentials and tuning the excitatory sigmoid parameters defining the mapping from voltage to firing rate. The first modification removes the pathological state, but predicts de-creasing alpha and delta power as drug concentration increases. The second modification predicts induction-emergence hysteresis (drug concentration is higher at induction than at emergence), but the alpha rhythm is lost, being replaced by a dominant delta-band oscillation.

text: Theoretical and experimental investigation of anaesthetic effects in the brain The main motivation of this study is to develop a better understanding of anaesthetic drug effects on brain dynamics including the paradoxical enhancement of seizure activity by some anaesthetic drugs. This thesis investigates two mean-field descriptions for the effect of general anaesthetic agents on brain activity: the extended Waikato cortical model (WM) and the Hindriks and van Putten (HvP) thalamocortical model. In the standard Waikato model, the population-average neuron voltage is determined by incoming activity at both electrical (gap-junction) and chemical synapses, the latter mediated by AMPA (excitatory) and GABAA (inhibitory) receptors. Here we extend the standard WM by including NMDA (excitatory) and GABAB (inhibitory) synapses. GABAergic anaesthetics, such as propofol, boost cortical inhibition by prolonging the tail of the unitary IPSP (inhibitory postsynaptic potential) at GABAA receptors, while increasing the synaptic gain at the slower-acting GABAB receptors. Dissociative anaesthetics act on NMDA receptors to give a voltage-dependent alteration of excitatory synaptic gain. We find that increasing GABAB or NMDA effect can alter the spatiotemporal dynamics of the standard WM, tending to suppress spatial (Turing) patterns in favour of temporal (Hopf) oscillations. The extended WM predicts increased susceptibility to seizure when GABAB effect is increased, particularly if the GABAergic agent reduces gap-junction diffusion. 
We tested these WM predictions with two biological experiments. We found that potentiation of GABAB receptors in slices of mouse cortical tissue tended to enhance seizure-like activity. However, our in vivo investigation of the effect of closure of gap junctions did not reveal any seizure patterns in mouse EEG signals. 
In the second part of this thesis, we present a detailed analysis of the HvP thalamocortical mean-field model for propofol anaesthesia. While we were able to confirm the Hindriks and van Putten predictions of increases in delta and alpha power at low levels of anaesthetic sedation, we find that for deeper anaesthetic effect, the model jumps from the low-firing state to an extremely high-firing stable state (~250 spikes/s), and remains stuck there even at GABAA prolongations as high as 300% which would be expected to induce full comatose suppression of all firing activity. To overcome this pathological behaviour, we tested two possible modifications: first, eliminating the population-dependent anaesthetic sensitivity (efficacy) of the HvP model; second, incorporating reversal potentials and tuning the excitatory sigmoid parameters defining the mapping from voltage to firing rate. The first modification removes the pathological state, but predicts de-creasing alpha and delta power as drug concentration increases. The second modification predicts induction-emergence hysteresis (drug concentration is higher at induction than at emergence), but the alpha rhythm is lost, being replaced by a dominant delta-band oscillation.

year: 2016

title: Reimagining communities of practice: Using relational frameworks to disrupt assumptions and inequity

authors: Fish, L

abstract: As theorised by Etienne Wenger, communities of practice are becoming settled as a framework for community engagement within Aotearoa New Zealand schools. In this article, the authors critically analyse the assumptions and inequities that can arise when communities of practice prioritise school values and staff comfort over the priorities of community participants and the knowledge they bring. The authors reference their experiences in communities of practice, using vignettes to explore tensions. The article argues that when schools draw authentically on Indigenous principles, including teu le vā, and use these to establish communities of practice, hospitable, equitable and productive relationships can be realised.

text: Reimagining communities of practice: Using relational frameworks to disrupt assumptions and inequity As theorised by Etienne Wenger, communities of practice are becoming settled as a framework for community engagement within Aotearoa New Zealand schools. In this article, the authors critically analyse the assumptions and inequities that can arise when communities of practice prioritise school values and staff comfort over the priorities of community participants and the knowledge they bring. The authors reference their experiences in communities of practice, using vignettes to explore tensions. The article argues that when schools draw authentically on Indigenous principles, including teu le vā, and use these to establish communities of practice, hospitable, equitable and productive relationships can be realised.

year: 2022-11-17

title: Representations of te reo Māori and te ao Māori in a translingual picturebook: How my Koro became a Star

authors: Barbour, Julie Renee

subjects: Indigenous language and culture

abstract: While English is the most commonly used language in Aotearoa New Zealand, it is a multilingual nation with two languages recognised as official: te reo Māori (the Māori language) and New Zealand Sign Language. The English language is dominant in children’s literature published in Aotearoa New Zealand, but since the 1980s there has been an increase in the number of picturebooks featuring two languages, te reo Māori and English. Previous work has explored how representations of te reo Māori and English in pukapuka pikitia reorua (dual language picturebooks) in Aotearoa reflect changing attitudes towards the two languages. In this article, we focus particularly on Brianne Te Paa and Story Hemi-Morehouse’s picturebook How my Koro became a Star. Originally written in te reo Māori, this multi-award winning picturebook is located at the beginning of Matariki, the Māori New Year celebration. In a move away from the linguistic analysis of te reo Māori being ‘borrowed’ by English, we consider how storytellers like Te Paa weave Māori language together with English in a translingual publication, supporting reader comprehension of Māori vocabulary and cultural meanings through embedded illustrations and explanations, inviting the curious reader to learn beyond the story.

text: Representations of te reo Māori and te ao Māori in a translingual picturebook: How my Koro became a Star While English is the most commonly used language in Aotearoa New Zealand, it is a multilingual nation with two languages recognised as official: te reo Māori (the Māori language) and New Zealand Sign Language. The English language is dominant in children’s literature published in Aotearoa New Zealand, but since the 1980s there has been an increase in the number of picturebooks featuring two languages, te reo Māori and English. Previous work has explored how representations of te reo Māori and English in pukapuka pikitia reorua (dual language picturebooks) in Aotearoa reflect changing attitudes towards the two languages. In this article, we focus particularly on Brianne Te Paa and Story Hemi-Morehouse’s picturebook How my Koro became a Star. Originally written in te reo Māori, this multi-award winning picturebook is located at the beginning of Matariki, the Māori New Year celebration. In a move away from the linguistic analysis of te reo Māori being ‘borrowed’ by English, we consider how storytellers like Te Paa weave Māori language together with English in a translingual publication, supporting reader comprehension of Māori vocabulary and cultural meanings through embedded illustrations and explanations, inviting the curious reader to learn beyond the story.

year: 2025