The relationship between variation in genes, GABA, structure and gamma oscillations in the visual and auditory system of healthy individuals and psychiatric disorder

Visual perception is highly variable across healthy individuals and increasing evidence suggests that this inter-individual variation could be due to differences at the genetic, neurochemical, structural and neurophysiological level. Specifically, variation in the GAD1 gene (responsible for synthesising the majority of cortical GABA) has been associated with differences in the level of the inhibitory neurotransmitter GABA. In addition, differences in GABA and cortical structural parameters (surface area and thickness) have been shown to predict differences in neural gamma oscillations. However, these findings have not been replicated in large independent studies. Hence, Chapter 3 and 4 of this thesis combines the non-invasive neuroimaging tools MRI, MRS and MEG with genetic data to investigate the relationship between variations in genes, GABA, structure and gamma oscillations in the visual cortex of a large cohort of healthy individuals. Group differences in GABA, structure and gamma oscillations have also been reported between psychiatric populations (schizophrenia and bipolar disorder) and healthy individuals.However, differences in the direction of effect (increase or decrease) and no group differences have been found. Thus, Chapter 5 aims to further study these inconsistent findings by exploring group differences in GABA, structure and gamma oscillations between a healthy group and a schizoaffective bipolar disorder group. Lastly, inter- individual variation is also present in auditory perception but has received much less attention into the factors driving this variation. As in the visual system, similar links between neurochemical, structural and neurophysiological measures could be present in the auditory domain. Chapter 6 investigates the association between auditory gamma oscillations and auditory structural parameters in a healthy cohort

Practitioner Insights Regarding Modern Slavery in Gloucestershire, UK

Slavery remains present in society and has been found to occur under various manifestations throughout the United Kingdom. Knowledge derived from academic enquiry regarding modern slavery has increased over recent years although sparse attention has been given to localised communities. It is important to develop the evidence-base locally to effectively increase the understanding of this diverse issue and aid local responses. This study aimed to produce evidence on local practitioners’ perspectives on modern slavery, focusing on the case study of Gloucestershire. Fourteen semi-structured interviews were conducted with a range of local practitioners in modern slavery related fields in Gloucestershire, including the police, healthcare and non-governmental organisations (NGOs). Thematic analysis was used to identify key themes from the data. These themes related to differing perceptions of the problem locally and numerous types of exploitation e.g. sexual exploitation, labour exploitation, criminal exploitation. One example of this is the alleged increase in sexual exploitation during a localised sporting event. The data also highlighted several barriers hindering local responses, progress and awareness e.g. victims not perceiving themselves as victims, victim co-operation with services and public service funding issues. This study contributes to the evidence indicating that localities such as Gloucestershire are not exempt from a variety of slavery practices. The enquiry highlights evidence of various types of slavery offences manifesting in Gloucestershire. However, a key finding of this study is the fragmented perceptions of localised modern slavery, which highlights the need to support a collaborative approach to this diverse problem. Barriers and complexities with the local response are acknowledged such as; concerns regarding local awareness, pressures associated with resourcing and the struggles associated with identifying victims of hidden criminality and exploitation. Although these findings relate to Gloucestershire they carry wider implications relevant to other localities across the UK. Due to the wider implications of this enquiry, a number of research, policy and practice recommendations are made based on the data from this study

Neurophysiologically-informed markers of individual variability and pharmacological manipulation of human cortical gamma

The ability to quantify synaptic function at the level of cortical microcircuits from non-invasive data would be enormously useful in the study of neuronal processing in humans and the pathophysiology that attends many neuropsychiatric disorders. Here, we provide proof of principle that one can estimate inter-and intra-laminar interactions among specific neuronal populations using induced gamma responses in the visual cortex of human subjects – using dynamic causal modelling based upon the canonical microcircuit (CMC; a simplistic model of a cortical column). Using variability in induced (spectral) responses over a large cohort of normal subjects, we find that the predominant determinants of gamma responses rest on recurrent and intrinsic connections between superficial pyramidal cells and inhibitory interneurons. Furthermore, variations in beta responses were mediated by inter-subject differences in the intrinsic connections between deep pyramidal cells and inhibitory interneurons. Interestingly, we also show that increasing the self-inhibition of superficial pyramidal cells suppresses the amplitude of gamma activity, while increasing its peak frequency. This systematic and nonlinear relationship was only disclosed by modelling the causes of induced responses. Crucially, we were able to validate this form of neurophysiological phenotyping by showing a selective effect of the GABA re-uptake inhibitor tiagabine on the rate constants of inhibitory interneurons. Remarkably, we were able to recover the pharmacodynamics of this effect over the course of several hours on a per subject basis. These findings speak to the possibility of measuring population specific synaptic function – and its response to pharmacological intervention – to provide subject-specific biomarkers of mesoscopic neuronal processes using non-invasive data. Finally, our results demonstrate that, using the CMC as a proxy, the synaptic mechanisms that underlie the gain control of neuronal message passing within and between different levels of cortical hierarchies may now be amenable to quantitative study using non-invasive (MEG) procedures

Voluntary disclosure of corporate strategy: determinants and outcomes. An empirical study into the risks and payoffs of communicating corporate strategy.

Business leaders increasingly face pressure from stakeholders to be transparent. There appears however little consensus on the risks and payoffs of disclosing vital information such as corporate strategy. To fill this gap, this study analyzes firm-specific determinants and organisational outcomes of voluntary disclosure of corporate strategy. Stakeholder theory and agency theory help to understand whether companies serve their interest to engage with stakeholders and overcome information asymmetries. I connect these theories and propose a comprehensive approach to measure voluntary disclosure of corporate strategy. Hypotheses from the theoretical framework are empirically tested through panel regression of data on identified determinants and outcomes and of disclosed strategy through annual reports, corporate social responsibility reports, corporate websites and corporate press releases by the 70 largest publicly listed companies in the Netherlands from 2003 through 2008. I found that industry, profitability, dual-listing status, national ranking status and listing age have significant effects on voluntary disclosure of corporate strategy. No significant effects are found for size, leverage and ownership concentration. On outcomes, I found that liquidity of stock and corporate reputation are significantly influenced by voluntary disclosure of corporate strategy. No significant effect is found for volatility of stock. My contributions to theory, methodology and empirics offers a stepping-stone for further research into understanding how companies can use transparency to manage stakeholder relations

Dasar dasar manajemen keuangan perusahaan

xxvii, 444 hlm.:ilus.: 26 c