The human primary motor cortex (M1) undergoes structural and functional change throughout life by a process known as neuroplasticity. Techniques which artificially induce neuroplastic changes are seen as potential adjunct therapies for neurological conditions reliant on neuroplasticity for recovery of function. Unfortunately, the reported improvements in function when these techniques have been used in combination with regular rehabilitation have so far been inconsistent. One reason attributed to this is the large variability in effectiveness of these techniques in inducing neuroplastic change. This thesis has investigated factors influencing the effectiveness and reproducibility of neuroplasticity induction in human M1 using several experimental paradigms. The effectiveness and reproducibility of inducing neuroplasticity in human M1 using two variants of a paired associative stimulation (PAS) protocol was investigated in the first set of experiments (Chapter 2). Both protocols repeatedly paired a peripheral electrical stimulus to the median nerve of the left wrist with single-pulse transcranial magnetic stimulation (TMS) delivered 25 ms later to the contralateral M1. Neuroplastic changes were quantified by comparing the amplitude of the muscle evoked potential (MEP) recorded in abductor pollicis brevis (APB) muscle by suprathreshold TMS prior to and following PAS. With both protocols, neuroplasticity induction was more effective, and the responses across sessions more reproducible, if the experiments were performed in the afternoon compared to the morning. Subsequent experiments confirmed the time of day modulation of PAS-induced neuroplasticity by repeatedly testing twenty-five subjects on two separate occasions, once in the morning (8 am), and once in the evening (8 pm) (Chapter 3). Time of day was also shown to modulate GABAergic inhibition in M1. In a further set of experiments, a double-blind, placebo-controlled study demonstrated that artificially elevated circulating cortisol levels (with a single oral dose of hydrocortisone) inhibits PAS-induced neuroplasticity in the evening (8 pm), indicating that the time of day modulation of neuroplasticity induction with PAS is due, at least in part, to differences in circulating cortisol levels (Chapter 3). The cortical circuits that are modulated by PAS have also been shown to be important in motor learning. Therefore, the final set of experiments, described in Chapter 4, investigated whether motor-training-related changes in motor performance (and cortical excitability) following a ballistic motor training task are also modulated by time of day. Twenty-two subjects repeatedly abducted their left thumb with maximal acceleration for thirty minutes during two experimental sessions (morning (8 am) and evening (8 pm)) on separate occasions. Motor training improved motor performance, and increased cortical excitability, however these changes were independent of time of day. It may be that the motor training task and/or outcome measures used were not sufficiently sensitive to detect a subtle time of day effect of motor training on motor performance. Alternatively, the normally functioning motor system may be able to compensate for changes in cortical excitability to maintain optimal motor performance. These findings have important implications for therapies reliant on neuroplasticity for recovery of function, and indicate that rehabilitation may be most effective when circulating cortisol levels are low. / Thesis (Ph.D.) - University of Adelaide, School of Molecular and Biomedical Science, 2009

No description available.

Direct cortico-motoneuronal (CM) connections of corticospinal tract neurons are a distinctive feature of the primate motor system which are known to be important for the capacity to perform independent finger movements. However, it is still unclear how the appropriate combinations of CM cells are recruited to produce the selective (fractionated) control over muscles of the upper limb that is necessary for independent finger movements. I have investigated whether GABAergic intracortical inhibitory (ICI) circuits in human motor cortex contribute to the selection of the appropriate CM cells during a motor task requiring selective activation of one of several intrinsic hand muscles. Behaviour of ICI circuits during voluntary contraction was compared for the dominant and non-dominant hemisphere of right-handed subjects, as hemispheric differences in ICI may contribute to preferential use of the right hand for fine motor tasks. Finally, I investigated the range of forces over which ICI contributes to selective activation of a hand muscle. Neurologically normal adult human subjects were recruited for all experiments. Surface electrodes recorded electromyographic activity of abductor pollicis brevis (APB), first dorsal interosseous and abductor digiti minimi muscles during controlled isometric contractions of APB at different force levels while subjects attempted to keep the other two muscles relaxed using visual feedback of EMG. Paired-pulse transcranial magnetic stimulation (TMS) was used to assess ICI at rest and during selective activation of a hand muscle. TMS intensity and interstimulus interval were varied in different trials. Data were compared for two different directions of induced current in the brain; posteriorly directed current (PA stimulation) and anteriorly directed current (AP stimulation). ICI is suppressed for corticospinal neurons controlling the muscle targeted for selective activation; no change in ICI was seen for corticospinal neurons controlling the muscles required to be relaxed. This indicates that differential modulation of ICI in human motor cortex contributes to selective activation of a hand muscle. The direction of current flow induced in the brain proved to be critical for demonstrating this effect. It was observed with AP stimulation but not PA stimulation. I argue that this is due to preferential activation by PA stimulation of interneurons producing I1 waves in corticospinal neurons. These interneurons are not acted upon by ICI circuits. This problem makes the conventional PA paired-pulse TMS technique unreliable for the assessment of ICI during voluntary contraction. With AP stimulation it was demonstrated that ICI is not modulated during weak selective activation of a hand muscle (&lt5percent of maximal voluntary contraction), but ICI effects on CM cells controlling the target muscle are progressively suppressed at higher levels of activation. The present study is the first to examine hemispheric differences in ICI during selective isometric contraction of an intrinsic hand muscle. No hemispheric differences were observed. These studies have demonstrated a functional role for ICI in fractionation of hand muscle activity in normal subjects. It also provides an improved basis for investigating the changes in ICI with TMS in various neurological conditions in which it has been reported that GABAergic inhibition is abnormal. / Thesis (Ph.D.)--School of Molecular and Biochemical Science, 2004.

Previous studies have shown that analogy instruction can be applied effectively in science education and motor skill acquisition; however, little is known about the application of analogy in speech motor performance. In four experiments, analogy instructions were tested in the speech domain. The first experiment (Chapter 2) used focus group methodology to establish a set of analogies that related pitch variation during speech production to a ‘waves at sea’ metaphor. The analogies were then used to elicit speech with different pitch variations. Analogy instructions were more effective than explicit instructions for eliciting speech with minimum pitch variation (i.e., monotonous speech). In the second experiment (Chapter 3), the influence of both analogy and explicit instructions on the perception of speech parameters invoked by maximum pitch variation was examined. Pitch variation in analogy instructed speech was perceived to be greater and more natural than when explicit instructions were provided. In the third experiment (Chapter 4), stress resistance in analogy instructed speech performance was evaluated. Analogy instructed speech performance was demonstrated to be significantly more stable under a psychologically stressful condition than explicitly instructed speech. The last experiment (Chapter 5), investigated the cognitive load of analogy on different components of the working memory system during speech performance. It was found that analogy instructions tended to place more cognitive load on the visual component of working memory than explicit instructions. The findings of the four experiments inform the application of analogy in speech motor skill performance in general, and contribute to understanding the mechanisms that underpin analogy within a working memory framework. The work also has significant potential for application in speech-language pathology treatment. / published_or_final_version / Human Performance / Doctoral / Doctor of Philosophy

Thesis (Ph.D.)--University of Iowa, 2009. / Thesis supervisors: Warrne G. Darling, Michel Ladouceur. Includes bibliographical references (leaves 116-131).

No description available.

published_or_final_version / Speech and Hearing Sciences / Doctoral / Doctor of Philosophy

The sensorimotor network receives a rich variety of somesthetic afferents and outputs considerable motor efferents, both of which drive experience-dependent plasticity in the system. It remains unclear to what extent subtle changes in somaesthesis and motor function extrinsic to the brain drive plasticity in the functional organisation and anatomy of the sensorimotor network. This thesis contains a series of multimodal MRI experiments to investigate how altered-use and disuse can induce plastic changes in the sensorimotor network of the human brain. In Chapter 3, a method of mapping digit somatotopy in primary somatosensory cortex at the single-subject level using 7.0 tesla fMRI was developed and applied for a study of healthy participants. Using a phase-encoding paradigm, digit representations were accurately mapped in under 10 minutes. These maps were reproducible over time and comparable to a standard block design. In Chapter 4, a further fMRI study assessed the potential for short-term reorganisation of digit representations in primary somatosensory cortex following a manipulation whereby the right index and right middle fingers were glued together for 24 hours. There was a marked shift in the cortical overlap of adjacent digits after the glued manipulation, not seen across an equivalent control period, providing strong evidence for short-term remapping of primary somatosensory cortex. In Chapter 5, a patient study investigated plasticity associated with chronic unilateral disuse of the upper limb. A cross-sectional comparison with control participants showed reduced grey matter density in the posterior right temporoparietal junction, and increased radial diffusivity in the white matter of the right superior longitudinal fasciculus, consistent with change in the right ventral attention network. A complementary longitudinal study in Chapter 6 investigated structural plasticity associated with rehabilitation of the disused limb. There were localised increases in grey matter density, notably in the right temporoparietal junction, further implicating a potential role for regions responsible for egocentric attention in regaining upper limb use. In Chapter 7, a further patient study investigated candidate predictive biomarkers at the sub-acute stage of stroke recovery, identifying CST-lesion cross-section and sensorimotor network strength as correlates of motor function, which warrant further study. The results of the studies presented in this thesis provide a novel insight into the nature and time frame of functional and structural plasticity associated with altered use and disuse. Further study of how subtle changes in our sensory and motor use shape the sensorimotor network is warranted, particularly in the context of disuse in non-neurological clinical populations.

Neural data often span multiple indices, such as neuron, experimental condition, trial, and time, resulting in a tensor or multidimensional array. Standard approaches to neural data analysis often rely on matrix factorization techniques, such as principal component analysis or nonnegative matrix factorization. Any inherent tensor structure in the data is lost when flattened into a matrix. Here, we analyze datasets from primary motor cortex from the perspective of tensor analysis, and develop a theory for how tensor structure relates to certain computational properties of the underlying system. Applied to the motor cortex datasets, we reveal that neural activity is best described by condition-independent dynamics as opposed to condition-dependent relations to external movement variables. Motivated by this result, we pursue one further tensor-related analysis, and two further dynamical systems-related analyses. First, we show how tensor decompositions can be used to denoise neural signals. Second, we apply system identification to the cortex- to-muscle transformation to reveal the intermediate spinal dynamics. Third, we fit recurrent neural networks to muscle activations and show that the geometric properties observed in motor cortex are naturally recapitulated in the network model. Taken together, these results emphasize (on the data analysis side) the role of tensor structure in data and (on the theoretical side) the role of motor cortex as a dynamical system.

The capacity of the adult human nervous system to alter the strength of connections between neurons and between networks of neurons is an exciting area of research providing novel insights into the mechanisms involved in learning, memory and recovery following brain damage. In recent years, it has become clear that both afferent input into the motor cortex and the learning of a new motor task can drive cortical reorganisation. This thesis is concerned with the functional significance of this plasticity, in both normal subjects and stroke patients, and with the question of whether stimulation - induced plasticity can lead to improved fine motor performance. My initial experiments were conducted to determine the optimal method of analysing responses to transcranial magnetic stimulation ( TMS ), and to investigate aspects of motor performance as the hand performs a precision task to grasp and lift an object. Studies on normal subjects showed that there is little difference between the dominant and non - dominant hands performing this task, but the type of grip used influences grip - force control. An investigation of stroke patients performing this task demonstrated that certain parameters were sensitive to differences between the affected and unaffected hands and these parameters were highly correlated with stroke - specific functional outcome measures. The induction of plastic change in the human motor cortex can be induced by repetition of movements, performing a complex motor task or stimulation of the peripheral afferents and / or the motor cortex itself. I observed that the application of so - called " associative stimulation " to two hand muscles in normal subjects increased the excitability of the corticospinal projection to those muscles, and improved performance times on a subsequent motor task to a greater extent than subjects receiving a control intervention. I then applied associative stimulation to the affected hand of stroke patients in conjunction with rehabilitation, which improved their ability to perform the dextrous grip - lift task. This is the first study to show that this method of inducing motor cortical plasticity can also lead to functional improvements in stroke patients. These studies confirm that using afferent stimulation to drive cortical reorganisation is associated with improved function and fine motor performance in both normal subjects and stroke patients. / Thesis (Ph.D.)--School of Molecular and Biomedical Science, 2006.