A Search For Principles of Basal Ganglia Function

The basal ganglia are a group of subcortical nuclei that contain about 100 million neurons in humans. Different modes of basal ganglia dysfunction lead to Parkinson's disease and Huntington's disease, which have debilitating motor and cognitive symptoms. However, despite intensive study, both the internal computational mechanisms of the basal ganglia, and their contribution to normal brain function, have been elusive. The goal of this thesis is to identify basic principles that underlie basal ganglia function, with a focus on signal representation, computation, dynamics, and plasticity. This process begins with a review of two current hypotheses of normal basal ganglia function, one being that they automatically select actions on the basis of past reinforcement, and the other that they compress cortical signals that tend to occur in conjunction with reinforcement. It is argued that a wide range of experimental data are consistent with these mechanisms operating in series, and that in this configuration, compression makes selection practical in natural environments. Although experimental work is outside the present scope, an experimental means of testing this proposal in the future is suggested. The remainder of the thesis builds on Eliasmith & Anderson's Neural Engineering Framework (NEF), which provides an integrated theoretical account of computation, representation, and dynamics in large neural circuits. The NEF provides considerable insight into basal ganglia function, but its explanatory power is potentially limited by two assumptions that the basal ganglia violate. First, like most large-network models, the NEF assumes that neurons integrate multiple synaptic inputs in a linear manner. However, synaptic integration in the basal ganglia is nonlinear in several respects. Three modes of nonlinearity are examined, including nonlinear interactions between dendritic branches, nonlinear integration within terminal branches, and nonlinear conductance-current relationships. The first mode is shown to affect neuron tuning. The other two modes are shown to enable alternative computational mechanisms that facilitate learning, and make computation more flexible, respectively. Secondly, while the NEF assumes that the feedforward dynamics of individual neurons are dominated by the dynamics of post-synaptic current, many basal ganglia neurons also exhibit prominent spike-generation dynamics, including adaptation, bursting, and hysterses. Of these, it is shown that the NEF theory of network dynamics applies fairly directly to certain cases of firing-rate adaptation. However, more complex dynamics, including nonlinear dynamics that are diverse across a population, can be described using the NEF equations for representation. In particular, a neuron's response can be characterized in terms of a more complex function that extends over both present and past inputs. It is therefore straightforward to apply NEF methods to interpret the effects of complex cell dynamics at the network level. The role of spike timing in basal ganglia function is also examined. Although the basal ganglia have been interpreted in the past to perform computations on the basis of mean firing rates (over windows of tens or hundreds of milliseconds) it has recently become clear that patterns of spikes on finer timescales are also functionally relevant. Past work has shown that precise spike times in sensory systems contain stimulus-related information, but there has been little study of how post-synaptic neurons might use this information. It is shown that essentially any neuron can use this information to perform flexible computations, and that these computations do not require spike timing that is very precise. As a consequence, irregular and highly-variable firing patterns can drive behaviour with which they have no detectable correlation. Most of the projection neurons in the basal ganglia are inhibitory, and the effect of one nucleus on another is classically interpreted as subtractive or divisive. Theoretically, very flexible computations can be performed within a projection if each presynaptic neuron can both excite and inhibit its targets, but this is hardly ever the case physiologically. However, it is shown here that equivalent computational flexibility is supported by inhibitory projections in the basal ganglia, as a simple consequence of inhibitory collaterals in the target nuclei. Finally, the relationship between population coding and synaptic plasticity is discussed. It is shown that Hebbian plasticity, in conjunction with lateral connections, determines both the dimension of the population code and the tuning of neuron responses within the coded space. These results permit a straightforward interpretation of the effects of synaptic plasticity on information processing at the network level. Together with the NEF, these new results provide a rich set of theoretical principles through which the dominant physiological factors that affect basal ganglia function can be more clearly understood

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

A Neurocomputational Model of the Functional Role of Dopamine in Stimulus-Response Task Learning and Performance

Thesis (Ph.D.) - Indiana University, Psychology, 2009The neuromodulatory neurotransmitter dopamine (DA) plays a complex, but central role in the learning and performance of stimulus-response (S-R) behaviors. Studies have implicated DA's role in reward-driven learning and also its role in setting the overall level of vigor or frequency of response. Here, a neurocomputational model is developed which models DA's influence on a set of brain regions believed to be involved in the learning and execution of S-R tasks, including frontal cortex, basal ganglia, and cingulate cortex. An `actor' component of the model is trained, using `babble' (random behavior selection) and `critic' (rewarding and punishing) components of the model, to perform acceptance/rejection responses upon presentation of color stimuli in the context of recently presented auditory tones. The model behaves like an autonomous organism learning (and relearning) through `trial-and-error'. The focus of the study, the impact of hypo- and hyper-normal DA activity on this model, is investigated by three different dopaminergic pathways--two striatal and one prefrontal cortical--being manipulated independently during the learning and performance of the color response task. Hypo-DA conditions, analogous to Parkinsonism, cause slowing and reduction of frequency of learned responses, and, at extremes, degrade the learning (either initial or reversal) of the task. Hyper-DA conditions, analogous to psychostimulant effects, cause more rapid response times, but also can lead to perseveration of incorrect learning of response on the task. The presence of these effects often depends on which DA-ergic pathway is manipulated, however, which has implications for interpretation of the pharmacological experimental data. The proposed model embodies an integrative theory of dopamine function which suggests that the base rate of DA cell activity encodes the overall `activity-oriented motivation' of the organism, with hunger and/or expectation of reward driving both response vigor and tendency to generate an explorative `babble' response. This more `tonic' feature of DA functionality coexists naturally with the more extensively-studied `phasic' reward-learning features. The model may provide better insights on the role of DA system dysfunction in the cognitive and motivational symptoms of disorders such as Parkinsonism, psychostimulant abuse, ADHD, OCD, and schizophrenia, accounting for deficits in both learning and performance of tasks

Final report key contents: main results accomplished by the EU-Funded project IM-CLeVeR - Intrinsically Motivated Cumulative Learning Versatile Robots

This document has the goal of presenting the main scientific and technological achievements of the project IM-CLeVeR. The document is organised as follows: 1. Project executive summary: a brief overview of the project vision, objectives and keywords. 2. Beneficiaries of the project and contacts: list of Teams (partners) of the project, Team Leaders and contacts. 3. Project context and objectives: the vision of the project and its overall objectives 4. Overview of work performed and main results achieved: a one page overview of the main results of the project 5. Overview of main results per partner: a bullet-point list of main results per partners 6. Main achievements in detail, per partner: a throughout explanation of the main results per partner (but including collaboration work), with also reference to the main publications supporting them

De animais a máquinas : humanos tecnicamente melhores nos imaginários de futuro da convergência tecnológica

Dissertação (mestrado)—Universidade de Brasília, Instituto de Ciências Sociais, Departamento de Sociologia, 2020.O tema desta investigação é discutir os imaginários sociais de ciência e tecnologia que emergem a partir da área da neuroengenharia, em sua relação com a Convergência Tecnológica de quatro disciplinas: Nanotecnologia, Biotecnologia, tecnologias da Informação e tecnologias Cognitivas - neurociências- (CT-NBIC). Estas áreas desenvolvem-se e são articuladas por meio de discursos que ressaltam o aprimoramento das capacidades físicas e cognitivas dos seres humanos, com o intuito de construir uma sociedade melhor por meio do progresso científico e tecnológico, nos limites das agendas de pesquisa e desenvolvimento (P&D). Objetivos: Os objetivos nesse cenário, são discutir as implicações éticas, econômicas, políticas e sociais deste modelo de sistema sociotécnico. Nos referimos, tanto as aplicações tecnológicas, quanto as consequências das mesmas na formação dos imaginários sociais, que tipo de relações se estabelecem e como são criadas dentro desse contexto. Conclusão: Concluímos na busca por refletir criticamente sobre as propostas de aprimoramento humano mediado pela tecnologia, que surgem enquanto parte da agenda da Convergência Tecnológica NBIC. No entanto, as propostas de melhoramento humano vão muito além de uma agenda de investigação. Há todo um quadro de referências filosóficas e políticas que defendem o aprimoramento da espécie, vertentes estas que se aliam a movimentos trans-humanistas e pós- humanistas, posições que são ao mesmo tempo éticas, políticas e econômicas. A partir de nossa análise, entendemos que ciência, tecnologia e política estão articuladas, em coprodução, em relação às expectativas de futuros que são esperados ou desejados. Ainda assim, acreditamos que há um espaço de diálogo possível, a partir do qual buscamos abrir propostas para o debate público sobre questões de ciência e tecnologia relacionadas ao aprimoramento da espécie humana.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)The subject of this research is to discuss the social imaginaries of science and technology that emerge from the area of neuroengineering in relation with the Technological Convergence of four disciplines: Nanotechnology, Biotechnology, Information technologies and Cognitive technologies -neurosciences- (CT-NBIC). These areas are developed and articulated through discourses that emphasize the enhancement of human physical and cognitive capacities, the intuition it is to build a better society, through the scientific and technological progress, at the limits of the research and development (R&D) agendas. Objectives: The objective in this scenery, is to discuss the ethic, economic, politic and social implications of this model of sociotechnical system. We refer about the technological applications and the consequences of them in the formation of social imaginaries as well as the kind of social relations that are created and established in this context. Conclusion: We conclude looking for critical reflections about the proposals of human enhancement mediated by the technology. That appear as a part of the NBIC technologies agenda. Even so, the proposals of human enhancement go beyond boundaries that an investigation agenda. There is a frame of philosophical and political references that defend the enhancement of the human beings. These currents that ally to the transhumanism and posthumanism movements, positions that are ethic, politic and economic at the same time. From our analysis, we understand that science, technology and politics are articulated, are in co-production, regarding the expected and desired futures. Even so, we believe that there is a space of possible dialog, from which we look to open proposals for the public discussion on questions of science and technology related to enhancement of human beings

Humanoid Robots

For many years, the human being has been trying, in all ways, to recreate the complex mechanisms that form the human body. Such task is extremely complicated and the results are not totally satisfactory. However, with increasing technological advances based on theoretical and experimental researches, man gets, in a way, to copy or to imitate some systems of the human body. These researches not only intended to create humanoid robots, great part of them constituting autonomous systems, but also, in some way, to offer a higher knowledge of the systems that form the human body, objectifying possible applications in the technology of rehabilitation of human beings, gathering in a whole studies related not only to Robotics, but also to Biomechanics, Biomimmetics, Cybernetics, among other areas. This book presents a series of researches inspired by this ideal, carried through by various researchers worldwide, looking for to analyze and to discuss diverse subjects related to humanoid robots. The presented contributions explore aspects about robotic hands, learning, language, vision and locomotion

Computational modelling of the human motor control system: Nonlinear enhancement of the adaptive model theory through simulation and experiment

Adaptive Model Theory (AMT) proposes that the brain forms and adaptively maintains inverse models of the world around it for adaptive feedforward control. This leading motor control theory unites principles of neurobiology, psychology and engineering. A modified version of AMT was developed with the capacity to control nonlinear systems, to predict signals with nonlinear statistical characteristics, and to perform simultaneous feedback and feedforward adaptive control. The modified version is called nonlinear Adaptive Model Theory or nAMT. An experimental study was also performed investigating inverse model formation in the human motor control system, the results of which were then compared with the nAMT model. A nonlinear dynamic system identification method was developed for nAMT to replace the linear structures employed by AMT. This method employs a neurobiologically-inspired locally-recurrent neural-network structure. A multi-layer adaptation algorithm was also developed specifically for this structure. Nonlinear AutoRegressive Moving-Average (NARMA) adaptive predictor structures replace the linear Moving Average (MA) predictor circuits used in AMT. Adaptive feedback control is augmented using a nonlinear dynamic forward model observer to improve the quality of the estimated response signal. Nonlinear dynamic inverse models are formed by placing the forward model in an internal feedback loop in which the gain function is adjusted to maintain stability. The internal inverse model motor-control hypothesis was tested experimentally in a study looking at human open-loop performance in a tracking task. The study was aimed at directly demonstrating the formation of an internal inverse model of a novel visuomotor relationship for feedforward control in the brain. The study involved 20 normal adult subjects who performed a pursuit random tracking task with a steering wheel for input. During learning the response cursor was periodically blanked, removing all feedback about the external system (i.e., about the relationship between hand motion and response cursor motion). Results showed a transfer of learning from the unblanked runs to the blanked runs for a static nonlinear system (14% median improvement between first 4 and last 4 runs, p = .001) thereby demonstrating adaptive feedforward control in the nervous system. No such transfer was observed for a dynamic linear system, indicating a dominant adaptive feedback control component. The observed open-loop responses showed a high-pass frequency response which could not be explained using traditional control-systems motor control models. Experimental results were compared with simulated results from the nAMT model. Results from the experimental study were used to verify and tune the computational model. The resulting simulations produced effects that mirrored the closed- and openloop characteristics of the experimental response trajectories. This supports the claim that an internal feedback loop is used for the inversion of external systems in the human brain. Other control-systems models (both AMT and feedback-error learning) would require substantial ad hoc modification to reproduce the observed disparity between closed- and open-loop results. In contrast, nAMT naturally reproduced the effect as a consequence of its novel nonlinear inversion method. In nAMT an inverse model is formed by embedding a forward model in an internal feedback loop incorporating a low derivative gain. The derivative loop-gain caused the inverse model to be relatively inaccurate at low frequencies, for which the feedback control loop was adequate, but to be increasingly accurate at higher frequencies. Maintenance of the loop-gain at the lowest possible levels maximizes the internal stability of the inverse. The simulation work confirmed that the nAMT model is capable of reproducing human behaviour under a wide range of conditions

Complexity, Emergent Systems and Complex Biological Systems:\ud Complex Systems Theory and Biodynamics. [Edited book by I.C. Baianu, with listed contributors (2011)]

An overview is presented of System dynamics, the study of the behaviour of complex systems, Dynamical system in mathematics Dynamic programming in computer science and control theory, Complex systems biology, Neurodynamics and Psychodynamics.\u

DYNAMIC SELF-ORGANISED NEURAL NETWORK INSPIRED BY THE IMMUNE ALGORITHM FOR FINANCIAL TIME SERIES PREDICTION AND MEDICAL DATA CLASSIFICATION

Artificial neural networks have been proposed as useful tools in time series analysis in a variety of applications. They are capable of providing good solutions for a variety of problems, including classification and prediction. However, for time series analysis, it must be taken into account that the variables of data are related to the time dimension and are highly correlated. The main aim of this research work is to investigate and develop efficient dynamic neural networks in order to deal with data analysis issues. This research work proposes a novel dynamic self-organised multilayer neural network based on the immune algorithm for financial time series prediction and biomedical signal classification, combining the properties of both recurrent and self-organised neural networks. The first case study that has been addressed in this thesis is prediction of financial time series. The financial time series signal is in the form of historical prices of different companies. The future prediction of price in financial time series enables businesses to make profits by predicting or simply guessing these prices based on some historical data. However, the financial time series signal exhibits a highly random behaviour, which is non-stationary and nonlinear in nature. Therefore, the prediction of this type of time series is very challenging. In this thesis, a number of experiments have been simulated to evaluate the ability of the designed recurrent neural network to forecast the future value of financial time series. The resulting forecast made by the proposed network shows substantial profits on financial historical signals when compared to the self-organised hidden layer inspired by immune algorithm and multilayer perceptron neural networks. These results suggest that the proposed dynamic neural networks has a better ability to capture the chaotic movement in financial signals. The second case that has been addressed in this thesis is for predicting preterm birth and diagnosing preterm labour. One of the most challenging tasks currently facing the healthcare community is the identification of preterm labour, which has important significances for both healthcare and the economy. Premature birth occurs when the baby is born before completion of the 37-week gestation period. Incomplete understanding of the physiology of the uterus and parturition means that premature labour prediction is a difficult task. The early prediction of preterm births could help to improve prevention, through appropriate medical and lifestyle interventions. One promising method is the use of Electrohysterography. This method records the uterine electrical activity during pregnancy. In this thesis, the proposed dynamic neural network has been used for classifying between term and preterm labour using uterine signals. The results indicated that the proposed network generated improved classification accuracy in comparison to the benchmarked neural network architectures

Algorithms for Neural Prosthetic Applications

abstract: In the last 15 years, there has been a significant increase in the number of motor neural prostheses used for restoring limb function lost due to neurological disorders or accidents. The aim of this technology is to enable patients to control a motor prosthesis using their residual neural pathways (central or peripheral). Recent studies in non-human primates and humans have shown the possibility of controlling a prosthesis for accomplishing varied tasks such as self-feeding, typing, reaching, grasping, and performing fine dexterous movements. A neural decoding system comprises mainly of three components: (i) sensors to record neural signals, (ii) an algorithm to map neural recordings to upper limb kinematics and (iii) a prosthetic arm actuated by control signals generated by the algorithm. Machine learning algorithms that map input neural activity to the output kinematics (like finger trajectory) form the core of the neural decoding system. The choice of the algorithm is thus, mainly imposed by the neural signal of interest and the output parameter being decoded. The various parts of a neural decoding system are neural data, feature extraction, feature selection, and machine learning algorithm. There have been significant advances in the field of neural prosthetic applications. But there are challenges for translating a neural prosthesis from a laboratory setting to a clinical environment. To achieve a fully functional prosthetic device with maximum user compliance and acceptance, these factors need to be addressed and taken into consideration. Three challenges in developing robust neural decoding systems were addressed by exploring neural variability in the peripheral nervous system for dexterous finger movements, feature selection methods based on clinically relevant metrics and a novel method for decoding dexterous finger movements based on ensemble methods.Dissertation/ThesisDoctoral Dissertation Bioengineering 201