http://hdl.handle.net/11343/159 Wed, 18 Jul 2018 22:46:22 GMT 2018-07-18T22:46:22Z http://hdl.handle.net/11343/214110 Decoding upper-limb kinematics from electrocorticography Nurse, Ewan Brain-computer interfaces (BCIs) are technologies for assisting individuals with motor impairments. Activity from the brain is recorded and then processed by a computer to control assistive devices. The prominent method for recording neural activity uses microelectrodes that penetrate the cortex to record from localized populations of neurons. This causes a severe inflammatory response, making this method unsuitable after approximately 1-2 years. Electrocorticography (ECoG), a method of recording potentials from the cortical surface, is a prudent alternative that shows promise as the basis of a clinically viable BCI. This thesis investigates aspects of ECoG relevant to the translation of BCI devices: signal longevity, motor information encoding, and decoding intended movement. Data was assessed from a first-in-human ECoG device trial to quantify changes in ECoG over multiple years. The mean power, calculated daily, was steady for all patients. It was demonstrated that the device could consistently record ECoG signal statistically distinct from noise up to approximately 100 Hz for the duration of the study. Therefore, long-term implanted ECoG can be expected to record movement-related high-gamma signals from humans for many years without deterioration of signal. ECoG was recorded from patients undertaking a two-dimensional center-out task. This data was used to generate encoder-decoder directional tuning models to describe and predict arm movement direction from ECoG. All four patients demonstrated channels that were significantly tuned to the direction of motion. Significant tuning was found across the cortex and was not focused on primary motor areas. Decoding significantly above chance with a population-vector approach was achieved in three of the four patients. Decoding accuracy was significantly improved by weighting the population vector by each channel's tuning signal-to-noise ratio. Hence, directional tuning exists in high-frequency ECoG during movement preparation, and movement angle can be decoded using population vector methods. Having confirmed the existence of direction-related information in the recorded data, artificial neural network models were created to decode intended movement direction. A convolutional neural network (CNN) model had significantly higher decoding accuracy than a fully connected model for all four patients for decoding movement direction. Training models on data from all patients and testing on a single patient improved decoding performance for all but the best performing patient with the CNN model. Decoding using data from multiple time-points with a CNN model and averaging the results boosted accuracy when using the mode of the outputs. Overall, it was demonstrated that artificial neural network models can decode intended movement direction from ECoG recordings of a two-dimensional center-out task. This thesis presents results that demonstrate ECoG has the desired signal properties for a clinically-relevant BCI. ECoG is shown to be robust over multiple years, encode direction-related information and can be decoded with high accuracy. © 2018 Dr. Ewan Nurse Sun, 01 Jan 2017 00:00:00 GMT http://hdl.handle.net/11343/214110 2017-01-01T00:00:00Z http://hdl.handle.net/11343/214105 Importin α1 plays an essential role in germline stem cell maintenance in the Drosophila testes Heaney, James Ronald The Drosophila testis maintains two stem cell populations at the apical tip, the germline stem cells and the cyst progenitor cells. 10-12 germline stem cells are arranged around the hub cells, a group of somatic cells responsible for maintaining the stem cell niche via expression of short range factors which promote self renewal and allow asymmetric cell division. A balance must be maintained between self renewal and differentiation to ensure the maintenance of the stem cells and production of mature spermatozoa. Spermatogenesis is a complex process requiring precise regulation to progress through the numerous stages required to produce viable spermatozoa. Importin α proteins act as adaptors between Importin β and target proteins to permit import of these target proteins. Metazoan genomes contain multiple Importin α proteins which have arisen due to multiple gene duplications and the different importin α genes show unique expression patterns during spermatogenesis in both Drosophila and mouse testes. It has been hypothesised that regulating importin α expression can drive the progression through the different stages of spermatogenesis through the targeted nuclear transport of different subsets of proteins into the nucleus. This project aims to investigate the role Importin α1 plays during spermatogenesis. It has been previously demonstrated that importin α1 null males are viable but sterile, the cause of this sterility remains unknown. To further investigate the role of Importin α1 during spermatogenesis I performed in-depth characterization of importin α1 null testes. I generated and characterised an importin α1 dominant negative transgene and used this transgene to screen for nuclear proteins that have their transport regulated by Importin α1. In this project I have shown that importin α1 is essential for the maintenance of germline stem cells in Drosophila testes and identified a potential target protein regulated by Importin α1 in spermatogonia. © 2018 Dr. James Ronald Heaney Sun, 01 Jan 2017 00:00:00 GMT http://hdl.handle.net/11343/214105 2017-01-01T00:00:00Z http://hdl.handle.net/11343/214104 Mental health of primary care attendees in Kota Kinabalu, Sabah Abdullah, Ahmad Faris This PhD thesis aims to investigate the mental health problems, care and service among the government clinics in Sabah, Malaysia, focusing on one of the most densely populated districts of Kota Kinabalu. Background behind undertaking of this project was based on existing epidemiological facts and studies from Sabah and peninsular Malaysia is presented. The lack of adequate mental health services, mental health research, poverty, immigration and other specific issues that are discussed in the literature review. This is a cross-sectional, general health clinic-based study among primary care attendees in the Kota Kinabalu district of Sabah. Aim: The study was designed to determine the prevalence of common mental disorders among primary care attendees in Kota Kinabalu and to identify the associated factors. It also determined the treatment gap, disability and perceived need for psychiatric treatment and care and mental health service utilization among primary care attendees with probable common mental disorder. Method: Simple random sampling method was used to select patients at three government general outpatient clinics. A total of four hundred and eighty-one patients were invited to participate. Four hundred and thirty agreed and fifty-one patients (10.6%) refused. Respondents were further interviewed by trained interviewers using a standard proforma to obtain socio-demographic data and clinical profile, Patient Health Questionnaire (PHQ), Work and Social Adjustment Scale (WSAS), General Practitioner User Perceived Need Questionnaire and Mental Health Service Utilization Questionnaire. Results: The prevalence of common mental disorders among primary care attendees were 52.1%, with 224 out of 430 respondents having a probable common mental disorder. This was higher than the previous two studies done in West Malaysia, where the prevalence of mental disorder in the primary care setting was found to be 24.7% and 26.7% respectively. Ninety-five respondents (22.1%) had more than one psychiatric diagnosis. Using univariate analysis: young age, female, monthly income less than RM1000 (1AUD=RM2.97), unemployment, student, secondary/tertiary education and recent stressors were all significantly associated with common mental disorder (PHQ positive). Using a logistic regression method, five factors were significantly predictive of common mental disorders. These were young age (18-29 years of age), female gender, higher education, income less than RM1000 and history of being physically or sexually victimized. Two hundred and nineteen (97.8%) out of two hundred and twenty-four respondents with common mental disorder had some form of disability. One hundred and sixty-three (72.8%) were slightly disabled, thirty-seven respondents (16.5%) were moderately disabled and nineteen (8.5%) were severely disabled. There was a significant and consistent positive association between the moderate disability and co-morbid common mental disorder in nearly all items of disability. The severely disabled group was shown to have a positive association with co-morbidity in two of five items of disability. These were private leisure activities and family relationship. Two hundred and five, out of two hundred and twenty-four respondents with a common mental disorder were not receiving any treatment. This was a treatment gap of 91.5%. Twenty-four respondents sought help from a traditional healer, twelve went to other professional mental health services and only three were seen by psychiatrist. Only four patients had been admitted to a psychiatric ward. The most sought out mental health services in this population were counselling (49.1%) and mental health information (41.1%). The least common mental health service provided was for medication (20.5%). The most common reason given for not accessing mental health services or treatment was “I preferred to manage myself the problem”. © 2018 Dr. Ahmad Faris Bin Abdullah Mon, 01 Jan 2018 00:00:00 GMT http://hdl.handle.net/11343/214104 2018-01-01T00:00:00Z http://hdl.handle.net/11343/214093 Electrophysiological and behavioural studies of top-down mechanisms of attention Kermani Ahangarani Farahani, Mojtaba Most modern skills, like driving a car, playing video games or reading a book, are relatively recent occurrences in human history and have presumably no specific hard-wired neural pathways. Instead, they piggyback on neural mechanisms that the brain evolved for other purposes, such as object recognition or visual attention. To take one specific example, reading is fundamental to function in modern daily life. It has been claimed that visuo-spatial attention is essential for selecting and binding strings of letters to identify words. In spite of half a century of extensive research on the mechanisms underlying visual processing, it is not well understood how cognitive abilities such as visual attention are related to reading. This thesis aimed to study not only the mutual interaction between reading and attention, but also first shed more light on the underlying neural mechanisms of visuospatial attention by investigating attention in one of our closest primate relatives. Study of electrical properties of several neurons surrounding an implanted microelectrode – known as extracellular recording – has been a robust method for basic understanding of how the nervous system works. However, performing this method in humans is unethical and as a result, electrophysiologists rely on recordings from animal brains, especially from the monkey as a species closely related to humans. Therefore, to understand further the neural mechanisms of top-down attention, I analysed electrophysiological neural signals which were recorded from macaques whilst they performed an attention-demanding task. I found two different parallel synchronized activities between posterior parietal and middle temporal cortices, one in the high- frequency range (high gamma) for feature discrimination and one in the low-frequency range (beta, low gamma) for attentional modulation. These results suggest that one process extracts and retains feature information, which is then used by a second process for top- down modulation of spatial attention. Although several theories have been suggested to explain how such oscillations in the neural activities reflect our performances in a particular cognitive function such as visual attention, the link between electrophysiology and psychophysics has not been fully studied. For the third experimental chapter, a slightly different version of the attention task was used from the one that earlier monkeys were trained on whilst collecting the data used for the first and second experiments. I found that reported oscillations in the neural activities in experiments one and two appear in the animal’s behaviour in a much lower frequency range: between 6 to 15 Hz. This rhythmicity in attention resembles fluctuations in the sampling of the external world by the visual system. It has been proposed that rhythmic allocation of attention is involved in the mechanisms of reading scripts. As such, languages with different scripts may therefore modulate attention differently. Using psychophysical tests, I found that visual attention is allocated asymmetrically depending on an individual’s habitual direction of reading. The results showed that efficiency of visuo-spatial attention mechanisms of left-to-right readers (such as English readers) and right-to-left readers (such as Farsi readers) were biased towards the right and left visual fields, respectively. On the other hand, bidirectional readers (fluent in both English and Farsi) were equally sensitive in the two hemifields. Search ability was not only found to be influenced by the habitual direction of reading, but such an influence could be modulated by even relatively short periods of reading. The improved visual attention was not accompanied by changes is oculomotor parameters i.e., fixation duration or saccade length. These findings provide evidence that the allocation of top-down attention in the visual field as measured by visual search ability can be influenced by the reading habit. The principle of rhythmic modulation of brain processes appears to underpin both visual attention as seen in common visual tasks as well as high level cognitive functions such as reading. The basic understanding of how complex, relatively modern, human functions are built upon processes inherited from evolution is likely to yield insights into the cause of many common ailments that affect human behaviour and indicate ways of managing them. © 2018 Dr Mojtaba Kermani Ahangarani Farahani Mon, 01 Jan 2018 00:00:00 GMT http://hdl.handle.net/11343/214093 2018-01-01T00:00:00Z