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Neuronal activities in the brain encode every decision, desire, or intention. Multiple brain regions are involved in translating intention into action. Detecting and decoding intentions directly from the brain could allow impaired individuals to communicate and interact with their environment despite central nervous system dysfunction. Brain-computer interface (BCI) systems access neuronal activities and translate them into actions using a computer. BCIs are used in research studies to replace, restore, or replace neuromuscular functions. In addition, BCIs provide new insights into how the brain works, aiding in new treatments for neurological conditions. BCI studies commonly target the primary motor cortex, the region of the brain most closely associated with volitional muscle control, with the expectation that signals from its neurons will be best suited for control of external effectors. Consequently, other brain regions are underrepresented in BCI studies. This thesis focuses on two brain regions in primates with access to higher-order control over intention and movement: The prefrontal cortex and the basal ganglia system. These areas are vital for naturalistic movement and must be more widely explored for decoding intentions. We aim to find the movement information while the intentions have yet to transfer into planning. One study in macaque monkeys explored eye movement intention, learning, and memory-related circuitry in the lateral prefrontal cortex (LPFC). In an eight-target saccade task, we could decode the target to which the monkeys would saccade before the eye movement began. Moreover, we decoded the abstract rule information acquired by the monkeys to find the correct target from the neuronal activities recorded from LPFC. In addition, the memory-related activities in LPFC were linked to monkeys' behaviour as evidence of the presence of working- and long-term memory circuitry in the prefrontal cortex. In another study on Parkinson's disease (PD) patients, we explored the possibility of volitional control of brain activities, which can lead to a self-induced procedure to reduce the symptoms of PD. We recorded the local field potentials (LFP) of the subthalamic nucleus (STN) of nine PD patients performing a cognitive task during deep brain stimulation surgery. The patients could modulate their brain activities to change the colour of a central sphere to match the colour of a peripheral cue in a virtual reality task. They modulated the signal power in beta frequencies (13-30 Hz) and the rate of beta bursts (the fast episodes of changing amplitude in a short period in LFP's beta frequencies) based on the task conditions. Both beta power and beta bursts are associated with the pathological state in PD patients. A decodable volitional modulation of both presents the STN as a valuable region for BCI studies which could lead to self-regulation of PD symptoms. The findings of this thesis contribute to the advancement of therapeutic systems used for various brain disorders like PD and Amyotrophic lateral sclerosis (ALS), as well as patients with disabilities that can benefit from assistive communicative technologies. The study on the LPFC increased the decoding accuracy of saccade intentions compared to previous studies. Additionally, decoding associative rules is beyond the complexity of previous studies. We also showed the effects of previously learned associations on the learning rate of new rules and how this memory-retrieved information modulates neuronal activities. Moreover, the study on the STN showed the volitional control of beta power and beta burst rates by PD patients, which can be used as therapeutic methods to improve the severity of the symptoms of PD.

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This paper provides an overview of the inspiration, research, and creative process involved in the composition of EverWind for orchestra and electronics. EverWind is based on field recordings from the American Southwest. The composition uses pitch material derived from spectral analysis of the recordings, and it incorporates a fixed media element using the field recordings that are then electronically manipulated to various degrees; this fixed media element is played alongside the orchestra. The paper also analyzes John Luther Adams' Dark Waves for Orchestra and Electronics and R. Murray Schafer's Music for Wilderness Lake in order to place EverWind within the broader musical context.

Thesis (DPhil (Drama))--Stellenbosch University, 2009. / The purpose of this study is to examine critically the phenomenon of participatory video and to situate within this the participatory video project that was initiated as part of this study in the informal settlement area of Kayamandi, South Africa. The overall objective of the dissertation is to consider the potential of participatory video within current-day South Africa towards enabling marginalised groups to represent themselves and achieve social change. As will be shown, the term ‘participatory video’ has been used broadly and applied to many different types of video products and processes. For the preliminary purposes of this dissertation, participatory video is defined as any video (or film) process dedicated to achieving change through which the subject(s) has been an integral part of the planning and/or production, as well as a primary end-user or target audience. The two key elements that distinguish participatory video are thus (1) understanding video (or film) as a tool for social change; and (2) understanding participation by the subject as integral to the video process. An historical analysis thus considers various filmmaking developments that fed into the emergence of participatory video. These include various film practices that used film as a tool for change -- from soviet agitprop through to the documentary movement of the 1930s, as well as various types of filmmaking in the 1960s that opened up questions of participation. The Fogo process, developed in the late 1960s, marked the start of participatory video and video advocacy and provided guiding principles for the Kayamandi project initiated as part of this dissertation. Practitioners of the Fogo process helped initiate participatory video practice in South Africa when they brought the process to South African anti-apartheid activists in the early 1970s. The Kayamandi Participatory Video Project draws on this background and context in its planned methodology and its implementation. Out of this, various theoretical issues arising from participatory video practice contextualise a reflection and an analysis of the Kayamandi project. Lastly, this study draws conclusions and recommendations on participatory video practice in South Africa.

In a rapidly changing visual environment, the delay between perception and action might impair the probability of survival of a prey or the efficiency of a predator. In order to compensate for delays associated with sensory-motor processing, primates often make predictions about future events and initiate anticipatory movements. To prepare an anticipatory movement, an estimation of when and where to a target is likely to move is necessary. Such an internal representation is often termed 'expectation'. The aim of this thesis was to investigate the gradual changes of a subject's expectation at the behavioral and electrophysiological levels. Anticipatory smooth pursuit was used in order to study temporal and directional changes in expectation. We found that temporal uncertainty strongly modulated the latency and the velocity of anticipatory movements suggesting that monkeys could estimate the hazard rate of target motion onset in order to decide when to initiate an anticipatory movement. In addition, we have shown that monkeys could use prior directional information in order to voluntarily initiate anticipatory responses in the direction of expected target motion. This prior directional information significantly affected the latency and velocity of these movements. Finally, we have shown that the majority of recorded supplementary eye field (SEF) neurons encoded expected target motion direction. The presence of a directional cue induced an increase of activity in the preferred direction of the neuron. Moreover, a large sub-population of neurons encoded the direction of future anticipatory movement. These results suggest that the SEF could be involved in the cognitive control of anticipatory pursuit eye movements when prior temporal and directional information is provided.

<p>Chronic pain is a distressing, prevalent, and expensive condition that is not well understood and difficult to treat. Spinal cord stimulation (SCS) has emerged as a viable means of managing chronic pain when conventional therapies are ineffective, but the efficacy of SCS has improved little since its inception. The mechanisms underlying SCS, in particular the neuronal responses to SCS, are not well understood, and prior efforts to optimize SCS have focused on electrode design and spatial selectivity without considering how the temporal aspects of SCS (stimulation frequency, pattern) may affect neuronal responses to stimulation. The lack of a biophysical basis in prior attempts to optimize therapy may have contributed to the plateau in the clinical efficacy of SCS over time. This dissertation combines computational modeling and in vivo electrophysiological approaches to investigate the effects of SCS on sensory neuron activity in the dorsal horn and uses the insights gained from these experiments to design novel temporal patterns for SCS that may be more effective than conventional therapy.</p><p>To study the mechanisms underlying SCS, we constructed a biophysically-based network model of the dorsal horn circuit consisting of interconnected dorsal horn interneurons and a wide dynamic range (WDR) projection neuron and representations of both local and surround receptive field inhibition. We validated the network model by reproducing cellular and network responses relevant to pain processing including wind-up, A-fiber mediated inhibition, and surround receptive field inhibition. To quantify experimentally the responses of spinal sensory projection neurons to SCS, we recorded the responses of antidromically identified sensory neurons in the lumbar spinal cord during 1-150 Hz SCS in both healthy rats and neuropathic rats following chronic constriction injury (CCI). In a subset of rats, we additionally assessed the impact of GABAergic inhibition on spinal neuron responses to SCS by conducting SCS experiments following the intrathecal administration of bicuculline, a GABAA receptor antagonist, and CGP 35348, a GABAB receptor antagonist. Finally, we used the computational model to design non-regular temporal patterns capable of inhibiting sensory neuron activity more effectively than conventional SCS and at lower equivalent stimulation frequencies than clinical standard 50 Hz SCS, and we experimentally validated model predictions of the improved efficacy of select patterns against conventional SCS.</p><p>Computational modeling revealed that the response of spinal sensory neurons to SCS depends on the SCS frequency; SCS frequencies of 30-100 Hz maximally inhibited the model WDR neuron consistent with clinical reports, while frequencies under 30 Hz and over 100 Hz excited the model WDR neuron. SCS-mediated inhibition was also dependent on GABAergic inhibition in the spinal cord: reducing the influence GABAergic interneurons by weakening their inputs or their connections to the model WDR neuron reduced the range of optimal SCS frequencies and changed the frequency at which SCS had a maximal effect. Experimentally, we observed that the relationship between SCS frequency and projection neuron activity predicted by the Gate Control circuit described a subset of observed SCS-frequency dependent responses but was insufficient to account for the heterogeneous responses measured experimentally. In addition, intrathecal administration of bicuculline, a GABAA receptor antagonist, increased spontaneous and evoked activity in projection neurons, enhanced excitatory responses to SCS, and reduced inhibitory responses to SCS, consistent with model predictions. Finally, computational modeling of dual frequency SCS, implemented by delivering two distinct frequencies simultaneously to distinct fiber populations, revealed frequency pairs that were more effective at inhibiting sensory neuron activity than equivalent conventional SCS and at lower average frequencies than clinically employed 50 Hz SCS. Experimental assessments of the effect of dual frequency SCS on spinal sensory neurons confirmed model predictions of greater efficacy at lower equivalent stimulation frequencies and suggest the use of non-regular temporal patterns as a novel approach to optimizing SCS. The outcomes of this dissertation are an improved understanding of the mechanisms underlying SCS, computational and experimental tools with which to continue the development and improvement of SCS. The insights and knowledge gained from the work described in this dissertation may result in translational applications that significantly improve the therapeutic outcomes of SCS and the quality of life of individuals affected by chronic pain.</p> / Dissertation

L'hippocampe est une région du cerveau située dans le lobe temporal médian. Avec d'autres structures limbiques, l'hippocampe est impliqué dans des processus d'apprentissage et de mémorisation et possède un rôle crucial dans le traitement spatial de l'information. Les synapses de l'hippocampe formées entre les fibres moussues (fm) originaires du gyrus denté et les neurones pyramidaux de CA3 ont reçu une attention particulière, compte tenu de la position stratégique occupée par le gyrus denté à l'entrée de l'hippocampe. En outre les synapses fm- CA3 sont distinctes de la plupart des autres synapses excitatrices du système nerveux central par leurs propriétés morphologiques et physiologiques uniques. Cela soulève la question de savoir si ces propriétés uniques reflètent aussi un rôle fonctionnel unique dans le traitement de l'information effectué par cette synapse au sein du microcircuit de l'hippocampe. Malheureusement nous ne savons que peu de choses sur la façon dont les cellules granulaires modulent l'activité des neurones de CA3 dans le réseau intact in vivo (Henze et al, 2002 ; Hagena et Manahan - Vaughan, 2010, 2011). Le manque d'information est dû au fait que la manipulation classique des circuits neuronaux par des approches électriques, pharmacologiques et génétiques manque de précisions spatiale et temporelle in vivo. L'utilisation de la stimulation extracellulaire de fibres moussues peut conduire à l'activation polysynaptique de cellules pyramidales de CA3, qui peuvent ensuite contaminer les réponses enregistrées. Par ailleurs, l'utilisation de critères trop conservateurs peut conduire à l'exclusion des réponses provenant des fibres moussues «purs» aux propriétés méconnues (Henze et al., 2000). Toutefois, le développement récent et rapide de l’optogénétique dans les neurosciences a fourni de nouveaux outils offrant une sélectivité spatiale élevée (activation optique spécifique de la cellule), et une grande précision temporelle (à l'échelle de la milliseconde), permettant la dissection et l'étude des circuits neuronaux in vivo. L'objectif de ma thèse était de mieux comprendre les mécanismes et les conséquences physiologiques de la plasticité synaptique à court terme se produisant à la synapse formée entre les fibres moussues et les neurones pyramidaux de CA3 dans le cerveau de souris intact. La présente thèse se compose de deux parties principales. Dans la première partie, j'ai exploré de nouveaux outils optogénétiques dans le but de contrôler l'activité des cellules granulaires à l’aide d’impulsions de lumière. La stimulation optogénétique repose sur l'activation du canal ionique channelrhodopsin - 2 - lumière fermée ( ChR2 ) par une lumière bleue et induit des potentiels d'action sur une large gamme de fréquences de stimulation. J'ai aussi observé que la stimulation optique peut être utilisée pour déclencher la plasticité à court terme au niveau des synapses fm-CA3.Dans la deuxième partie j'ai affiné la méthodologie de stimulation optogénétique in vivo pour la caractérisation non invasive du fonctionnement synaptique des synapses fm- CA3. La fiabilité de la stimulation optogénétique d'une population neuronale génétiquement ciblée ainsi que la résolution d'une seule cellule obtenue en utilisant des enregistrements de cellules entières sont des étapes importantes vers une meilleure compréhension du rôle fonctionnel des fibres moussues dans le réseau de l'hippocampe in vivo. / The hippocampus is a brain region located in the medial temporal lobe. Along with other limbic structures, the hippocampus is involved in learning and memory processes and has a crucial role in spatial information processing. Within the hippocampus synapses made between mossy fibers (mf) originating from the dentate gyrus and CA3 pyramidal neurons have received particular attention, given the strategic position occupied by the dentate gyrus at the entrance of the hippocampus. Moreover mf-CA3 synapses are distinct from most of other excitatory synapses in the central nervous system for their unusual morphological and physiological properties. This raises the question if these unique properties reflect a unique functional role in information processing carried out by this synapse within the microcircuit of the hippocampus. Unfortunately very little is known on how granule cells modulate the activity of CA3 neurons in the intact network in vivo (Henze et al., 2002; Hagena and Manahan-Vaughan, 2010, 2011). The paucity of information is due to the fact that classical manipulation of neuronal circuits using electrical, pharmacological and genetic approaches lack spatial and temporal precision in vivo. The use of bulk extracellular stimulation may lead to polysynaptic activation of CA3 pyramidal cells, which can subsequently contaminate putative mossy fibers synaptic responses measured in CA3 pyramidal cells. The use of overly conservative criteria on the other side may lead to the exclusion of “pure” mossy fibers responses with unexpected properties (Henze et al., 2000).However the recent and fast growth of optogenetics in neuroscience has provided new tools with high spatial selectivity (cell specific optical activation) and temporal precision (at the millisecond scale), allowing the dissection and investigation of neuronal circuits in vivo. The aim of my thesis was to gain insight into the mechanisms and the physiological consequences of short-term synaptic plasticity occurring at mossy fibers to CA3 pyramidal neurons synapses in the intact mouse brain. The present thesis consists of two main parts. In the first part I explored new optogenetic tools to control the activity of granule cells with pulses of light. Optogenetic stimulation, which relies on the activation of the light-gated ion channel channelrhodopsin-2 (ChR2) by blue light reliably induced action potentials over a wide range of frequencies of stimulation. I also found that optical stimulation can be used to trigger short term plasticity at mf-CA3 synapses. In the second part I refined optogenetic stimulation methodology in vivo for non-invasive characterization of synaptic functioning of the mf-CA3 synapses. The reliability of optogenetic stimulation of a genetically targeted neuronal population together with the single cell resolution obtained using whole-cell recordings are important steps towards a better understanding of the functional role of the mossy fibers in the hippocampal network in vivo.