The onset of motor learning impairments in Parkinson's disease: a computational investigation.

The basal ganglia (BG) is part of a basic feedback circuit regulating cortical function, such as voluntary movements control, via their influence on thalamocortical projections. BG disorders, namely Parkinson's disease (PD), characterized by the loss of neurons in the substantia nigra, involve the progressive loss of motor functions. At the present, PD is incurable. Converging evidences suggest the onset of PD-specific pathology prior to the appearance of classical motor signs. This latent phase of neurodegeneration in PD is of particular relevance in developing more effective therapies by intervening at the earliest stages of the disease. Therefore, a key challenge in PD research is to identify and validate markers for the preclinical and prodromal stages of the illness. We propose a mechanistic neurocomputational model of the BG at a mesoscopic scale to investigate the behavior of the simulated neural system after several degrees of lesion of the substantia nigra, with the aim of possibly evaluating which is the smallest lesion compromising motor learning. In other words, we developed a working framework for the analysis of theoretical early-stage PD. While simulations in healthy conditions confirm the key role of dopamine in learning, in pathological conditions the network predicts that there may exist abnormalities of the motor learning process, for physiological alterations in the BG, that do not yet involve the presence of symptoms typical of the clinical diagnosis.

A paradigm for emulating the early learning stage of handwriting: Performance comparison between healthy controls and Parkinson's disease patients in drawing loop shapes.

We present a novel paradigm, aimed at emulating the early stage of handwriting learning in proficient writers, by asking them to produce a familiar shape through a novel (unfamiliar) motor plan. Handwriting of beginner writers is characterized by slower movements, reduced spatial precision, lower fluency and reduced force regulation compared to those observed in the handwriting production of proficient writers. Features observed in the ink trace obtained with the novel motor plan and performance comparison of the handwriting obtained by familiar and unfamiliar motor plan suggest that the proposed paradigm is able to elicit non-automated movements in proficient writers. As that produced by beginner writers, handwriting of Parkinson's disease (PD) patients is characterized by lack of fluency, slowness and abrupt changes of direction. Furthermore, PD patients show impaired performance in learning novel motor behaviors, as well as in executing motor behaviors acquired before the onset of the disease. We used the proposed paradigm for comparing the performance achieved by healthy controls in writing a familiar shape through a novel motor plan with those obtained by PD patients performing a well-known motor plan for drawing the same shape. Our analysis points out some similarities between performance obtained by healthy controls and those obtained by PD patients, sustaining the hypothesis that the fine tuning of the motor plan parameters involved in the handwriting production is impaired by PD.