A mathematical model of levodopa medication effect on basal ganglia in parkinson’s disease: An application to the alternate finger tapping task

Malfunctions in the neural circuitry of the basal ganglia (BG), induced by alterations in the dopaminergic system, are responsible for an array of motor disorders and milder cognitive issues in Parkinson's disease (PD). Recently Baston and Ursino (2015a) presented a new neuroscience mathematical model aimed at exploring the role of basal ganglia in action selection. The model is biologically inspired and reproduces the main BG structures and pathways, modeling explicitly both the dopaminergic and the cholinergic system. The present work aims at interfacing this neurocomputational model with a compartmental model of levodopa, to propose a general model of medicated Parkinson's disease. Levodopa effect on the striatum was simulated with a two-compartment model of pharmacokinetics in plasma joined with a motor effect compartment. The latter is characterized by the levodopa removal rate and by a sigmoidal relationship (Hill law) between concentration and effect. The main parameters of this relationship are saturation, steepness, and the half-maximum concentration. The effect of levodopa is then summed to a term representing the endogenous dopamine effect, and is used as an external input for the neurocomputation model; this allows both the temporal aspects of medication and the individual patient characteristics to be simulated. The frequency of alternate tapping is then used as the outcome of the whole model, to simulate effective clinical scores. Pharmacokinetic-pharmacodynamic modeling was preliminary performed on data of six patients with Parkinson's disease (both “stable” and “wearing-off” responders) after levodopa standardized oral dosing over 4 h. Results show that the model is able to reproduce the temporal profiles of levodopa in plasma and the finger tapping frequency in all patients, discriminating between different patterns of levodopa motor response. The more influential parameters are the Hill coefficient, related with the slope of the effect sigmoidal relationship, the drug concentration at half-maximum effect, and the drug removal rate from the effect compartment. The model can be of value to gain a deeper understanding on the pharmacokinetics and pharmacodynamics of the medication, and on the way dopamine is exploited in the neural circuitry of the basal ganglia in patients at different stages of the disease progression

Involvement of the cortico-basal ganglia-thalamocortical loop in developmental stuttering

Stuttering is a complex neurodevelopmental disorder that has to date eluded a clear explication of its pathophysiological bases. In this review, we utilize the Directions Into Velocities of Articulators (DIVA) neurocomputational modeling framework to mechanistically interpret relevant findings from the behavioral and neurological literatures on stuttering. Within this theoretical framework, we propose that the primary impairment underlying stuttering behavior is malfunction in the cortico-basal ganglia-thalamocortical (hereafter, cortico-BG) loop that is responsible for initiating speech motor programs. This theoretical perspective predicts three possible loci of impaired neural processing within the cortico-BG loop that could lead to stuttering behaviors: impairment within the basal ganglia proper; impairment of axonal projections between cerebral cortex, basal ganglia, and thalamus; and impairment in cortical processing. These theoretical perspectives are presented in detail, followed by a review of empirical data that make reference to these three possibilities. We also highlight any differences that are present in the literature based on examining adults versus children, which give important insights into potential core deficits associated with stuttering versus compensatory changes that occur in the brain as a result of having stuttered for many years in the case of adults who stutter. We conclude with outstanding questions in the field and promising areas for future studies that have the potential to further advance mechanistic understanding of neural deficits underlying persistent developmental stuttering.R01 DC007683 - NIDCD NIH HHS; R01 DC011277 - NIDCD NIH HHSPublished versio

Multimodal Grounding for Language Processing

This survey discusses how recent developments in multimodal processing facilitate conceptual grounding of language. We categorize the information flow in multimodal processing with respect to cognitive models of human information processing and analyze different methods for combining multimodal representations. Based on this methodological inventory, we discuss the benefit of multimodal grounding for a variety of language processing tasks and the challenges that arise. We particularly focus on multimodal grounding of verbs which play a crucial role for the compositional power of language.Comment: The paper has been published in the Proceedings of the 27 Conference of Computational Linguistics. Please refer to this version for citations: https://www.aclweb.org/anthology/papers/C/C18/C18-1197

A Defence of Cartesian Materialism

One of the principal tasks Dennett sets himself in "Consciousness Explained" is to demolish the Cartesian theatre model of phenomenal consciousness, which in its contemporary garb takes the form of Cartesian materialism: the idea that conscious experience is a process of presentation realized in the physical materials of the brain. The now standard response to Dennett is that, in focusing on Cartesian materialism, he attacks an impossibly naive account of consciousness held by no one currently working in cognitive science or the philosophy of mind. Our response is quite different. We believe that, once properly formulated, Cartesian materialism is no straw man. Rather, it is an attractive hypothesis about the relationship between the computational architecture of the brain and phenomenal consciousness, and hence one that is worthy of further exploration. Consequently, our primary aim in this paper is to defend Cartesian materialism from Dennett's assault. We do this by showing that Dennett's argument against this position is founded on an implicit assumption (about the relationship between phenomenal experience and information coding in the brain), which while valid in the context of classical cognitive science, is not forced on connectionism

Predictive coding accelerates word recognition and learning in the early stages of language development

The ability to predict future events in the environment and learn from them is a fundamental component of adaptive behavior across species. Here we propose that inferring predictions facilitates speech processing and word learning in the early stages of language development. Twelve- and 24-month olds' electrophysiological brain responses to heard syllables are faster and more robust when the preceding word context predicts the ending of a familiar word. For unfamiliar, novel word forms, however, word-expectancy violation generates a prediction error response, the strength of which significantly correlates with children's vocabulary scores at 12 months. These results suggest that predictive coding may accelerate word recognition and support early learning of novel words, including not only the learning of heard word forms but also their mapping to meanings. Prediction error may mediate learning via attention, since infants' attention allocation to the entire learning situation in natural environments could account for the link between prediction error and the understanding of word meanings. On the whole, the present results on predictive coding support the view that principles of brain function reported across domains in humans and non-human animals apply to language and its development in the infant brain. A video abstract of this article can be viewed at: http://hy.fi/unitube/video/e1cbb495-41d8-462e-8660-0864a1abd02c. [Correction added on 27 January 2017, after first online publication: The video abstract link was added.]Peer reviewe

Development of a Large-Scale Integrated Neurocognitive Architecture - Part 2: Design and Architecture

In Part 1 of this report, we outlined a framework for creating an intelligent agent based upon modeling the large-scale functionality of the human brain. Building on those results, we begin Part 2 by specifying the behavioral requirements of a large-scale neurocognitive architecture. The core of our long-term approach remains focused on creating a network of neuromorphic regions that provide the mechanisms needed to meet these requirements. However, for the short term of the next few years, it is likely that optimal results will be obtained by using a hybrid design that also includes symbolic methods from AI/cognitive science and control processes from the field of artificial life. We accordingly propose a three-tiered architecture that integrates these different methods, and describe an ongoing computational study of a prototype 'mini-Roboscout' based on this architecture. We also examine the implications of some non-standard computational methods for developing a neurocognitive agent. This examination included computational experiments assessing the effectiveness of genetic programming as a design tool for recurrent neural networks for sequence processing, and experiments measuring the speed-up obtained for adaptive neural networks when they are executed on a graphical processing unit (GPU) rather than a conventional CPU. We conclude that the implementation of a large-scale neurocognitive architecture is feasible, and outline a roadmap for achieving this goal

Towards a dynamic theory of intentions

In this paper, I offer a sketch of a dynamic theory of intentions. I argue that several categories or forms of intentions should be distinguished based on their different (and complementary) functional roles and on the different contents or types of contents they involve. I further argue that an adequate account of the distinctive nature of actions and of their various grades of intentionality depends on a large part on a proper understanding of the dynamic transitions among these different forms of intentions. One further benefit of this approach is to open the way to a more perspicuous account of the phenomenology of action and of the role of conscious thought in the production of action

Dynamic coordination in brain and mind

Our goal here is to clarify the concept of 'dynamic coordination', and to note major issues that it raises for the cognitive neurosciences. In general, coordinating interactions are those that produce coherent and relevant overall patterns of activity, while preserving the essential individual identities and functions of the activities coordinated. 'Dynamic coordination' is the coordination that is created on a moment-by-moment basis so as to deal effectively with unpredictable aspects of the current situation. We distinguish different computational goals for dynamic coordination, and outline issues that arise concerning local cortical circuits, brain systems, cognition, and evolution. Our focus here is on dynamic coordination by widely distributed processes of self-organisation, but we also discuss the role of central executive processes