Artificial metaplasticity prediction model for cognitive rehabilitation outcome in acquired brain injury patients

Objective The main purpose of this research is the novel use of artificial metaplasticity on multilayer perceptron (AMMLP) as a data mining tool for prediction the outcome of patients with acquired brain injury (ABI) after cognitive rehabilitation. The final goal aims at increasing knowledge in the field of rehabilitation theory based on cognitive affectation. Methods and materials The data set used in this study contains records belonging to 123 ABI patients with moderate to severe cognitive affectation (according to Glasgow Coma Scale) that underwent rehabilitation at Institut Guttmann Neurorehabilitation Hospital (IG) using the tele-rehabilitation platform PREVIRNEC©. The variables included in the analysis comprise the neuropsychological initial evaluation of the patient (cognitive affectation profile), the results of the rehabilitation tasks performed by the patient in PREVIRNEC© and the outcome of the patient after a 3–5 months treatment. To achieve the treatment outcome prediction, we apply and compare three different data mining techniques: the AMMLP model, a backpropagation neural network (BPNN) and a C4.5 decision tree. Results The prediction performance of the models was measured by ten-fold cross validation and several architectures were tested. The results obtained by the AMMLP model are clearly superior, with an average predictive performance of 91.56%. BPNN and C4.5 models have a prediction average accuracy of 80.18% and 89.91% respectively. The best single AMMLP model provided a specificity of 92.38%, a sensitivity of 91.76% and a prediction accuracy of 92.07%. Conclusions The proposed prediction model presented in this study allows to increase the knowledge about the contributing factors of an ABI patient recovery and to estimate treatment efficacy in individual patients. The ability to predict treatment outcomes may provide new insights toward improving effectiveness and creating personalized therapeutic interventions based on clinical evidence

Data mining applied to the cognitive rehabilitation of patients with acquired brain injury

Acquired brain injury (ABI) is one of the leading causes of death and disability in the world and is associated with high health care costs as a result of the acute treatment and long term rehabilitation involved. Different algorithms and methods have been proposed to predict the effectiveness of rehabilitation programs. In general, research has focused on predicting the overall improvement of patients with ABI. The purpose of this study is the novel application of data mining (DM) techniques to predict the outcomes of cognitive rehabilitation in patients with ABI. We generate three predictive models that allow us to obtain new knowledge to evaluate and improve the effectiveness of the cognitive rehabilitation process. Decision tree (DT), multilayer perceptron (MLP) and general regression neural network (GRNN) have been used to construct the prediction models. 10-fold cross validation was carried out in order to test the algorithms, using the Institut Guttmann Neurorehabilitation Hospital (IG) patients database. Performance of the models was tested through specificity, sensitivity and accuracy analysis and confusion matrix analysis. The experimental results obtained by DT are clearly superior with a prediction average accuracy of 90.38%, while MLP and GRRN obtained a 78.7% and 75.96%, respectively. This study allows to increase the knowledge about the contributing factors of an ABI patient recovery and to estimate treatment efficacy in individual patients

Machine learning for the prediction of psychosocial outcomes in acquired brain injury

Acquired brain injury (ABI) can be a life changing condition, affecting housing, independence, and employment. Machine learning (ML) is increasingly used as a method to predict ABI outcomes, however improper model evaluation poses a potential bias to initially promising findings (Chapter One). This study aimed to evaluate, with transparent reporting, three common ML classification methods. Regularised logistic regression with elastic net, random forest and linear kernel support vector machine were compared with unregularised logistic regression to predict good psychosocial outcomes after discharge from ABI inpatient neurorehabilitation using routine cognitive, psychometric and clinical admission assessments. Outcomes were selected on the basis of decision making for care packages: accommodation status, functional participation, supervision needs, occupation and quality of life. The primary outcome was accommodation (n = 164), with models internally validated using repeated nested cross-validation. Random forest was statistically superior to logistic regression for every outcome with areas under the receiver operating characteristic curve (AUC) ranging from 0.81 (95% confidence interval 0.77-0.85) for the primary outcome of accommodation, to its lowest performance for predicting occupation status with an AUC of 0.72 (0.69-0.76). The worst performing ML algorithm was support vector machine, only having statistically superior performance to logistic regression for one outcome, supervision needs, with an AUC of 0.75 (0.71-0.80). Unregularised logistic regression models were poorly calibrated compared to ML indicating severe overfitting, unlikely to perform well in new samples. Overall, ML can predict psychosocial outcomes using routine psychosocial admission data better than other statistical methods typically used by psychologists

Data mining applied to neurorehabilitation data

Tese de mestrado integrado, Engenharia Biomédica e Biofísica (Engenharia Clínica e Instrumentação Médica) Universidade de Lisboa, Faculdade de Ciências, 2017Apesar de não serem a principal causa de morte no Mundo, as lesões cerebrais são talvez a principal razão de existirem tantos casos de pessoas que veem a sua vida quotidiana afetada. Tal acontece devido a grandes dificuldades cognitivas que podem ser derivadas de um acidente de automóvel, de uma queda, da presença de um tumor, de um acidente vascular cerebral, da exposição a substâncias tóxicas ou de uma outra qualquer situação que tenha envolvido uma lesão do cérebro. De entre este tipo de lesões podem considerar-se aquelas que são provenientes de traumas por forças externas, ou seja, as chamadas lesões cerebrais traumáticas ou traumatismos crânio-encefálicos. É precisamente em pessoas que sofreram uma lesão desse tipo que se foca este estudo. Em pessoas que, depois dessas lesões, foram sujeitas a um tratamento de neuro reabilitação. Este tratamento, baseado na realização de tarefas especialmente desenhadas para estimular a reorganização das ligações neuronais, permite que os doentes tenham a possibilidade de voltar a conseguir realizar tarefas do dia-a-dia com a menor dificuldade possível. O objetivo da realização destas tarefas é a estimulação da capacidade de plasticidade cerebral, responsável pelo desenvolvimento das conexões sinápticas desde o nascimento e que permite ao cérebro voltar a estabelecer o seu funcionamento normal depois de uma lesão. Naturalmente, o grau de afetação de uma pessoa depende do tipo de lesão e tem uma grande influência não só no tempo de recuperação física e mental, como também no seu estado final. O estudo documentado neste relatório de estágio constitui um meio para atingir um objetivo comum a outros trabalhos de investigação nesta área; pretende-se que os tratamentos de neuro reabilitação possam vir a ser personalizados para cada paciente, para que a sua recuperação seja otimizada. A ideia é que, conhecendo alguns dos dados pessoais de um doente, considerando informação sobre o seu estado inicial e através dos resultados de testes realizados, seja possível associá-lo a um determinado perfil disfuncional, de características bastante específicas, para o terapeuta poder adaptar o seu tratamento. O Institut Guttmann, em Barcelona, foi o primeiro hospital espanhol a prestar cuidados a doentes de lesões medulares. Hoje em dia, um dos seus muitos projetos chama-se GNPT Guttmann NeuroPersonalTrainer e leva a casa dos seus doentes uma plataforma que lhes permite realizar as tarefas definidas pelos terapeutas, no âmbito dos seus tratamentos de neuro reabilitação. Dados desses doentes, incluindo informação démica e resultados de testes realizados antes e depois dos tratamentos, foram cedidos pelo Institut Guttmann ao Grupo de Biomédica e Telemedicina (GBT) sob a forma de bases de dados. Através da sua análise e utilizando ferramentas de Data Mining foi possível obter perfis gerais de disfunção cognitiva e descrever a evolução desses perfis, o principal objetivo desta dissertação. Encontrar padrões em grandes volumes de dados é a principal função de um processo de Data Mining, tratando o assunto de forma muito genérica. Na verdade, é este o conceito utilizado quando são abordados temas de extração de conhecimento a partir de grandes quantidades de dados. Há diversas técnicas que o permitem fazer, que utilizam algoritmos baseados em funções estatísticas e redes neuronais e que têm vindo a ser melhoradas ao longo dos últimos anos, desde que surgiu a primeira necessidade de lidar com grandes conjuntos de elementos. O propósito é sempre o mesmo: que a análise feita a partir destas técnicas permita converter a informação oculta dos dados em informação que pode ser depois utilizada para caracterizar populações, tomar decisões ou para validar resultados. Neste caso, foram utilizados algoritmos de Clustering, um método de Data Mining que permite obter grupos de elementos semelhantes entre si, os clusters, considerando as características de cada um destes elementos. Dados de 698 doentes que sofreram um traumatismo craniano e cuja informação disponível nas bases de dados fornecidas pelo Institut Guttmann satisfazia todas as condições necessárias para serem considerados no estudo, foram integrados num Data Warehouse - um depósito de armazenamento de dados - e depois estruturados. A partir de funções criadas em SQL - a principal linguagem de consultas e organização de bases de dados relacionais - foram obtidas as pontuações correspondentes aos testes realizados pelos doentes, antes do início do tratamento e depois de este ser terminado. Estes testes visaram avaliar, utilizando cinco diferentes níveis de pontuação correspondentes a cada grau de afetação (0 para sem afetação, 1 para afetação suave, 2 para afetação moderada, 3 para afetação severa e 4 para afetação aguda), três funções estritamente relacionadas com o nível cognitivo, a atenção, a memória e algumas funções executivas. As pontuações obtidas para cada uma das funções constituem uma média ponderada da pontuação cada uma das subfunções (atenção dividida, atenção seletiva, memória de trabalho, entre outras), calculadas por pelo menos um dos 24 itens de avaliação a que cada pessoa foi sujeita. De seguida, foram determinados os grupos iniciais e finais, recorrendo a uma ferramenta muito útil para encontrar correlações em grandes conjuntos de dados, o software SPSS. Para determinar a constituição dos clusters iniciais foi aplicado um algoritmo de Clustering designado K-means e, para os finais, um outro denominado TwoStep. A principal característica desta técnica descritiva de Data Mining é a utilização da distância como medida de verificação da proximidade entre dois elementos de um cluster. Os seus algoritmos diferem no tipo de dados a que se aplicam e também na forma como calculam os agrupamentos de elementos. Para cada um dos clusters, e de acordo com cada uma das funções, foi observada a distribuição das pontuações, através de gráficos de barras. Foram também confrontados ambos os conjuntos de clusters para se poder interpretar a relação entre eles. Os clusters, que neste contexto correspondem a perfis de afetação cognitiva, foram validados, e concluiu-se que permitem descrever bem a população em estudo. Por um lado, os seis clusters iniciais determinados representam de uma forma fiel, e com muito sentido do ponto de vista clínico, os conjuntos de pessoas com características suficientemente definidas que os distinguem entre si. Já os três clusters finais, usados para retratar a população no final do tratamento e analisar as evoluções dos pacientes, retratam perfis bastante opostos, o que permitiu, de certa forma interpretar com maior facilidade para que pacientes o efeito da neuro-reabilitação foi mais ou menos positivo. Alguns estudos citados no estado de arte revelaram que algumas variáveis são suscetíveis de influenciar o estado final de um doente. Aproveitando a existência de dados suficientes para tal, foi observado se, tendo em conta os clusters finais, se poderia fazer alguma inferência sobre o efeito de algumas das variáveis – incluindo a idade, o nível de estudos, o intervalo de tempo entre a lesão e o início do tratamento e a sua duração – em cada um destes. No final, considerando apenas as pontuações dos testes em cada função, antes e depois dos tratamentos, foram analisados e interpretados, recorrendo a gráficos, os desenvolvimentos e a evolução global de cada doente. Como desenvolvimentos possíveis, foram tidos em conta os casos em que houve melhorias, agravamentos e também os casos em que os doentes mantiveram o seu estado. Fazendo uso da informação sobre a forma como evoluíram os pacientes, foi possível verificar se, de facto, utilizando apenas os valores das pontuações obtidas nos testes, se poderia ou não confirmar que outras variáveis poderiam ter efeitos na determinação do estado final de um paciente. Os gráficos obtidos demonstraram que há diferenças muito subtis considerando algumas das variáveis, principalmente entre os dos doentes que melhoraram e os dos doentes que viram a sua condição agravada. Concluiu-se que o facto de os clusters agruparem pessoas com tipos de evolução diferentes levou a que o efeito de outras variáveis se mostrasse muito disperso. O tipo de investigação sugerido para futuros desenvolvimentos inclui: (i) o estudo das outras hipóteses de perfis apresentados pelo software usado (SPSS); (ii) considerar os diferentes aspetos das funções avaliadas a um nível mais detalhado; (iii) ter em conta outras variáveis com possíveis efeitos no estado final de um doente.Although they are not the leading cause of death in the world, brain injuries are perhaps the main reason why there are so many cases of people who see their daily lives affected. This is due to the major cognitive difficulties that appear after brain lesion. Brain injuries include those that are derived from traumas due to external forces – the traumatic brain injuries. This study is focused in people who, after these injuries, were subjected to a neuro rehabilitation treatment. The treatment, based on tasks specially designed to stimulate the reorganization of neural connections, allows patients to regain their abilities to perform their everyday tasks with the least possible difficulty. These tasks aim to stimulate the brain plasticity capacity, responsible for the development of synaptic connections which allows the brain to re-establish its normal functioning after an injury. The study documented in this internship report constitutes another step for a major goal, common to other studies in this area: that neuro rehabilitation treatments can be personalized for each patient, so that their recovery is optimized. Knowing some of the personal data of a patient, considering information about their initial state and through the results of tests performed, it is possible to assign a person to a certain dysfunctional profile, with specific characteristics and for the therapist to adapt treatment. One of his many projects of the Institut Guttmann (IG) is called GNPT Guttmann NeuroPersonalTrainer and brings into its patients’ home a platform that allows them to perform the tasks set by the therapists in the context of their neurorehabilitation treatments. Data from these patients, including clinical information and test results performed before and after the treatment, were provided by the IG to the Biomedical and Telemedicine Group (GBT) as databases. Through its analysis and using Data Mining techniques it was possible to obtain general profiles of cognitive dysfunction and to characterize the evolution of these profiles, the objective of this work. Finding patterns and extracting knowledge from large volumes of data are the main functions of a Data Mining process. An analysis performed using these techniques enables the conversion of information hidden in data into information that can later be used to make decisions or to validate results. In this case, Clustering algorithms, which build groups of elements with the similar characteristics called clusters, were used. Also, data from 698 patients who suffered brain trauma and whose information available in the databases provided by the IG satisfied all the conditions considered necessary were integrated into a Data Warehouse and then structured. The scores corresponding to the tests performed before and after the treatment were calculated, for each patient. These tests aimed to evaluate, using five different punctuation levels corresponding to each degree of affectation, three functions strictly related to cognitive level: attention, memory and some executive functions (cognitive processes necessary for the cognitive control of behavior). The initial and final clusters, representing patients’ profiles, were determined, using the SPSS software. The distribution of the scores over the clusters was observed through bar graphs. Both groups of clusters were also confronted to interpret the relationship between them. The clusters, which in this context correspond to profiles of cognitive affectation, were validated, and it was concluded that, at this moment, they represent well the state of patients under study. As some variables, like age and study level, are likely to influence the final state of a patient, it was observed if, given the final clusters, some inference could be made about the effect of those variables. No valuable conclusions were taken from this part. Also, considering the tests scores, patients’ evolution was identified as improvements, aggravations and cases where the conditions is maintained. Using that information, conclusions were extracted, regarding the population and the variables effect. The plots obtained allowed us to correctly describe the patients’ evolution and also to see if the variables considered were good descriptors of that evolution. A simple interpretation from of the facts allows to conclude that the calculated are good general, but not perfect descriptors of the population. The type of research suggested for future developments includes: (i) the study of the other hypothesis of profiles presented by the Data Mining software; (ii) consider the different aspects of the functions evaluated at a more detailed level; (iii) take into account other variables with possible effects on describing the final state of a patient

Metaplasticity A Promising Tool to Disentangle Chronic Disorders of Consciousness Differential Diagnosis

The extent of cortical reorganization after brain injury in patients with Vegetative State/Unresponsive Wakefulness Syndrome (UWS) and Minimally Conscious State (MCS) depends on the residual capability of modulating synaptic plasticity. Neuroplasticity is largely abnormal in patients with UWS, although the fragments of cortical activity may exist, while patients MCS show a better cortical organization. The aim of this study was to evaluate cortical excitability in patients with disorders of consciousness (DoC) using a transcranial direct current stimulation (TDCS) metaplasticity protocol. To this end, we tested motor-evoked potential (MEP) amplitude, short intracortical inhibition (SICI), and intracortical facilitation (ICF). These measures were correlated with the level of consciousness (by the Coma Recovery Scale-Revised, CRS-R). MEP amplitude, SICI, and ICF strength were significantly modulated following different metaplasticity TDCS protocols only in the patients with MCS. SICI modulations showed a significant correlation with the CRS-R score. Our findings demonstrate, for the first time, a partial preservation of metaplasticity properties in some patients with DoC, which correlates with the level of awareness. Thus, metaplasticity assessment may help the clinician in differentiating the patients with DoC, besides the clinical evaluation. Moreover, the responsiveness to metaplasticity protocols may identify the subjects who could benefit from neuromodulation protocols

Supporting the design of sequences of cumulative activities impacting on multiple areas through a data mining approach : application to design of cognitive rehabilitation programs for traumatic brain injury patients

Traumatic brain injury (TBI) is a leading cause of disability worldwide. It is the most common cause of death and disability during the first three decades of life and accounts for more productive years of life lost than cancer, cardiovascular disease and HIV/AIDS combined. Cognitive Rehabilitation (CR), as part of Neurorehabilitation, aims to reduce the cognitive deficits caused by TBI. CR treatment consists of sequentially organized tasks that require repetitive use of impaired cognitive functions. While task repetition is not the only important feature, it is becoming clear that neuroplastic change and functional improvement only occur after a number of specific tasks are performed in a certain order and repetitions and does not occur otherwise. Until now, there has been an important lack of well-established criteria and on-field experience by which to identify the right number and order of tasks to propose to each individual patient. This thesis proposes the CMIS methodology to support health professionals to compose CR programs by selecting the most promising tasks in the right order. Two contributions to this topic were developed for specific steps of CMIS through innovative data mining techniques SAIMAP and NRRMR methodologies. SAIMAP (Sequence of Activities Improving Multi-Area Performance) proposes an innovative combination of data mining techniques in a hybrid generic methodological framework to find sequential patterns of a predefined set of activities and to associate them with multi-criteria improvement indicators regarding a predefined set of areas targeted by the activities. It combines data and prior knowledge with preprocessing, clustering, motif discovery and classes` post-processing to understand the effects of a sequence of activities on targeted areas, provided that these activities have high interactions and cumulative effects. Furthermore, this work introduces and defines the Neurorehabilitation Range (NRR) concept to determine the degree of performance expected for a CR task and the number of repetitions required to produce maximum rehabilitation effects on the individual. An operationalization of NRR is proposed by means of a visualization tool called SAP. SAP (Sectorized and Annotated Plane) is introduced to identify areas where there is a high probability of a target event occurring. Three approaches to SAP are defined, implemented, applied, and validated to a real case: Vis-SAP, DT-SAP and FT-SAP. Finally, the NRRMR (Neurorehabilitation Range Maximal Regions) problem is introduced as a generalization of the Maximal Empty Rectangle problem (MER) to identify maximal NRR over a FT-SAP. These contributions combined together in the CMIS methodology permit to identify a convenient pattern for a CR program (by means of a regular expression) and to instantiate by a real sequence of tasks in NRR by maximizing expected improvement of patients, thus provide support for the creation of CR plans. First of all, SAIMAP provides the general structure of successful CR sequences providing the length of the sequence and the kind of task recommended at every position (attention tasks, memory task or executive function task). Next, NRRMR provides specific tasks information to help decide which particular task is placed at each position in the sequence, the number of repetitions, and the expected range of results to maximize improvement after treatment. From the Artificial Intelligence point of view the proposed methodologies are general enough to be applied in similar problems where a sequence of interconnected activities with cumulative effects are used to impact on a set of areas of interest, for example spinal cord injury patients following physical rehabilitation program or elderly patients facing cognitive decline due to aging by cognitive stimulation programs or on educational settings to find the best way to combine mathematical drills in a program for a specific Mathematics course.El traumatismo craneoencefálico (TCE) es una de las principales causas de morbilidad y discapacidad a nivel mundial. Es la causa más común de muerte y discapacidad en personas menores de 30 años y es responsable de la pérdida de más años de vida productiva que el cáncer, las enfermedades cardiovasculares y el SIDA sumados. La Rehabilitación Cognitiva (RC) como parte de la Neurorehabilitación, tiene como objetivo reducir el impacto de las condiciones de discapacidad y disminuir los déficits cognitivos causados (por ejemplo) por un TCE. Un tratamiento de RC está formado por un conjunto de tareas organizadas de forma secuencial que requieren un uso repetitivo de las funciones cognitivas afectadas. Mientras que el número de ejecuciones de una tarea no es la única característica importante, es cada vez más evidente que las transformaciones neuroplásticas ocurren cuando se ejecutan un número específico de tareas en un cierto orden y no ocurren en caso contrario. Esta tesis propone la metodología CMIS para dar soporte a los profesionales de la salud en la composición de programas de RC, seleccionando las tareas más prometedoras en el orden correcto. Se han desarrollado dos contribuciones para CMIS mediante las metodologías SAMDMA y RNRRM basadas en técnicas innovadoras de minería de datos. SAMDMA (Secuencias de Actividades que Mejoran el Desempeño en Múltiples Áreas) propone una combinación de técnicas de minería de datos y un marco de trabajo genérico híbrido para encontrar patrones secuenciales en un conjunto de actividades y asociarlos con indicadores de mejora multi-criterio en relación a un conjunto de áreas hacia las cuales las actividades están dirigidas. Combina el uso de datos y conocimiento experto con técnicas de pre-procesamiento, clustering, descubrimiento de motifs y post procesamiento de clases. Además, se introduce y define el concepto de Rango de NeuroRehabilitación (RNR) para determinar el grado de performance esperado para una tarea de RC y el número de repeticiones que debe ejecutarse para producir mayores efectos rehabilitadores. Se propone una operacionalización del RNR por medio de una herramienta de visualización llamada Plano Sectorizado Anotado (PAS). PAS permite identificar áreas en las que hay una alta probabilidad de que ocurra un evento. Tres enfoques diferentes al PAS se definen, implementan, aplican y validan en un caso real : Vis-PAS, DT-PAS y FT-PAS. Finalmente, el problema RNRRM (Rango de NeuroRehabilitación de Regiones Máximas) se presenta como una generalización del problema del Máximo Rectángulo Vacío para identificar RNR máximos sobre un FT-PAS. La combinación de estas dos contribuciones en la metodología CMIS permite identificar un patrón conveniente para un programa de RC (por medio de una expresión regular) e instanciarlo en una secuencia real de tareas en RNR maximizando las mejoras esperadas de los pacientes, proporcionando soporte a la creación de planes de RC. Inicialmente, SAMDMA proporciona la estructura general de secuencias de RC exitosas para cada paciente, proporcionando el largo de la secuencia y el tipo de tarea recomendada en cada posición. RNRRM proporciona información específica de tareas para ayudar a decidir cuál se debe ejecutar en cada posición de la secuencia, el número de veces que debe ser repetida y el rango esperado de resultados para maximizar la mejora. Desde el punto de vista de la Inteligencia Artificial, ambas metodologías propuestas, son suficientemente generales como para ser aplicadas a otros problemas de estructura análoga en que una secuencia de actividades interconectadas con efectos acumulativos se utilizan para impactar en un conjunto de áreas de interés. Por ejemplo pacientes lesionados medulares en tratamiento de rehabilitación física, personas mayores con deterioro cognitivo debido al envejecimiento y utilizan programas de estimulación cognitiva, o entornos educacionales para combinar ejercicios de cálculo en un programa específico de Matemáticas

Motor learning and neuroplasticity in humans

The central nervous system is plastic, in that the number and strength of synaptic connections changes over time. In the adult the most important driver of such changes is experience, in the form of learning and memory. There are thought to be a number of rules, operating relatively local to each synapse that govern changes in strength and organisation. Some of these such as Hebbian plasticity or plasticity following repeated activation of a connection have been studied in detail in animal preparations. However, recent work with non-invasive methods of transcranial stimulation in human, such as transcranial magnetic stimulation, has opened the opportunity to study similar effects in the conscious human brain. In this thesis I use these methods to explore some of the presumed changes in synaptic connectivity in the motor cortex during different forms of motor learning. The experiments only concern learning in the healthy brain; however it seems likely that the same processes will be relevant to neurorehabilitation and disease of the nervous system. This thesis explores the link between neuroplasticity and motor learning in humans using non-invasive brain stimulation, pharmacological agents and psychomotor testing in 6 related studies. 1) Chapter 3 reports initial pharmacological investigations to confirm the idea that some of the long term effects of TMS are likely to involve LTP-like mechanisms. The study shows that NMDA agonism can affect the response to a repetitive form of TMS known as theta burst stimulation (TBS) 2) Following up on the initial evidence for the role of NMDA receptors in the long term effects of TBS, Chapter 4 explores the possible modulatory effects of dopaminergic drugs on TBS. 3) Chapter 5 takes the investigations to normal behaviours by examining how the NMDA dependent plasticity produced by TBS interacts with learning a simple motor task of rapid thumb abduction. The unexpected results force a careful examination of the possible mechanisms of motor learning in this task. 4) Chapter 6 expands on these effects by employing a battery of TMS methods as well as drug agents to examine the role of different intracortical circuits in ballistic motor learning. 5) Chapter 7 studies the plasticity of intracortical circuits involved in transcallosal inhibition. 6) Chapter 8 studies the interaction between synaptic plasticity invoked by TBS and sequence learning. The studies described in the thesis contribute to understanding of how motor learning and neuroplasticity interact, and possible strategies to enhance these phenomena for clinical application

The Effects of Galvanic Vestibular Stimulation on Motor Cortical Excitability

Galvanic vestibular stimulation (GVS) can reduce the symptoms of numerous neurological conditions including episodic migraine, parkinsonism, acquired prosopagnosia and hemi-spatial neglect. Despite these preliminary findings, the mechanism underlying these therapeutic effects are still poorly understood. Functional imaging conducted during GVS indicates a potential change in cortical activation across widespread regions of the brain. However, these imaging studies are limited because they lack a functional correlate and rely on a relatively crude and poorly localised measure of excitability. The current study aimed to investigate the effects of GVS on cortical excitability via the more precise markers of TMS-induced motor-evoked potentials (MEPs) and movement-related cortical potentials (MRCPs), surrogate markers of long-term potentiation (LTP) and long-term depression (LTD) which are often compromised in neurological patients. Experiment 1 (N = 40) examined the effects of 25 minutes 1mA noisy, bipolar GVS on MEPs in the minutes and subsequent day after stimulation. Relative to sham, GVS reduced MEP amplitude 24 hours following stimulation for all participants who showed high cortical excitability at baseline. Experiment 2 (N = 24) followed a similar pre-post design to Experiment 1, however, the effects of GVS on the MRCP were measured via the Bereitschaftspotential (BP) while participants performed voluntary finger movements. Most likely owing to methodological shortcomings, Experiment 2 failed to obtain a BP response at baseline so did not enable the study hypothesis to be assessed. Experiment 3 was designed to both address these potential shortcomings and increase clinical relevance, recruiting a single individual with right hemisphere chronic stroke. A BP at baseline was observed but there was no evidence of GVS modulation. In sum, whilst Experiments 2 and 3 yielded few novel insights, the results of Experiment 1 indicate that GVS inhibits cortical excitability, potentially reflecting LTD-like effects. This observation may help explain its reported therapeutic benefits and also suggests that is should be applied to other disorders that involve cortical hyper-excitability

Neurophysiological investigation of auditory augmentation to facilitate observational learning of everyday actions

This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel UniversityThis thesis explores the neurophysiology of auditory augmentation of observed actions, and its effects on motor learning, neural activity, and plasticity. To this end, three studies were conducted. In the first study, we used Transcranial Magnetic Stimulation (TMS) to determine the effects of practising a motor task via sonification of combined action observation and motor imagery (sAOMI) on corticospinal excitability, compared to practising without extrinsic auditory information. In addition, we aimed at probing practice-dependent audiomotor plasticity. To this extent we used a variation of a commonly used method to probe and induce plasticity in humans, auditory paired associative stimulation (aPAS). Practice significantly increased corticospinal excitability, but sonification did not affect it. In addition, while aPAS completed alone significantly modulated corticospinal excitability, when practice primed aPAS, no neuromodulation was found. In a follow-up study, we explored the effects of sAOMI on corticospinal excitability during action observation (AO) or AOMI of the same action, and whether sonification induced audiomotor resonance, which is usually interpreted as development of an audiomotor association. The results corroborated and extended the findings of the previous study: practice increased corticospinal excitability at rest and during AO and AOMI, but sonification did not affect it. In addition, with sonification did not induce an audiomotor association. In a third study, we used electroencephalography (EEG) and other psychophysical measures, including a motor imagery questionnaire and mental chronometry, to assess changes resulting from practising with sonified action observation, followed by motor imagery of the same action. After two practice sessions, performance and kinaesthetic motor imagery vividness significantly improved, and participants’ mental chronometry was significantly more aligned with the speed of the observed action, compared to pre-practice measures. Sonification did not induce changes in any measure. EEG analysis revealed that participants who practised with sonification were able to sustain event-related desynchronization (ERD) in the lower alpha band (7-10 Hz) for longer, compared to participants who practices without sonification. No changes in higher alpha (10-12 Hz) or Beta (16-25 Hz) bands were found. Taken together, convergent results from this thesis suggest that sonified action observation has little effect on neurophysiological and behavioural markers of motor imagery ability and performance in healthy individuals. On the other hand, practising with sonified action observation may induce attentional modulations that enhance the learner’s ability to sustain action-related attentional processing for longer. We discuss these results in the context of contemporary neurocomputational theories of perception and action